Alshehri et al. The authors characterized 26 phytochemical compounds from the leaf extract of A. obesum related to antioxidant activity evaluated for different methods. Noteworthy, the extract toxicity on tumoral cells was confirmed by the decrease in viability, fragmentation and nuclear condensation of A lung cancer cells.

In addition, the potential anti-inflammatory activity of the extract was evidenced by the reduction in the levels of main inflammatory mediators in murine alveolar macrophages after treatment with the extract. These significant results contribute to further studies aiming to formulate herbal-based medicine.

In a study elegantly designed, Zhang et al. demonstrated the anti-glioma activity of new juglone derivatives, an antitumor pigment used for years in herbal medicine. The authors performed in vitro and in vivo experiments using U87 and cell lines and human glioblastoma cells in mice orthotopic model, respectively.

The derivatives were more stable than natural juglone and less susceptible to oxidation, preserving the antitumoral activity. Derivatives with allyl or butyl substitution were most effective, inhibiting the proliferation and inducing apoptosis of glioma cells mediated by ROS.

This Research Topic also includes the important work of Tang et al. Under another approach, the authors demonstrated that the hepatoxicity of Sunitinib, a multi-targeted tyrosine kinase inhibitor with remarkable anticancer activity, may be protected by glycyrrhetinic acid.

Sunitinib reduced the viability of nontumoral hepatocytes mediated by the activation of mitogen-activated proteins kinases MAPKs due to the exacerbation of ROS production. The apoptosis and autophagy induced by Sunitib were relieved by the treatment with glycyrrhetinic acid.

According to the authors, glycyrrhetinic acid could be a preventive therapy to reduce liver injury caused by Sunitinib.

In a study characterized by a robust experimental design, Rahimifard et al. Furthermore, the treatment suppressed telomerase activity, pro-inflammatory gene expression, and cell invasion.

These findings highlight the potential clinical utility of cisplatin-resveratrol combination in the management of cancer. This area of research also encompasses the important contributions made by Liu et al. Platinum-based chemotherapy induces cancer cell death by elevating oxidative stress levels to a cytotoxic extent.

Liu et al. have identified a noteworthy association between the CAT rs polymorphism and platinum-based chemotherapy-related progression-free survival in patients with lung cancer, indicating its potential as a prognostic biomarker for such patients.

A pioneering review by Li et al. has uncovered the importance of ROS in regulating multiple signaling pathways. Online ISBN : eBook Packages : Biomedical and Life Sciences Biomedical and Life Sciences R0.

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Policies and ethics. Skip to main content. Abstract Increased oxidative stress is a common feature observed in many different types of cancer.

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References Ahmed KM, Cao N, Li JJ HER-2 and NF-kappaB as the targets for therapy-resistant breast cancer. Anticancer Res 26 6B — CAS PubMed Central PubMed Google Scholar Aykin-Burns N et al Increased levels of superoxide and H 2 O 2 mediate the differential susceptibility of cancer cells versus normal cells to glucose deprivation.

Biochem J 1 —37 CAS PubMed Central PubMed Google Scholar Babior BM NADPH oxidase: an update. Blood 93 5 — CAS PubMed Google Scholar Bae YS et al Platelet-derived growth factor-induced H 2 O 2 production requires the activation of phosphatidylinositol 3-kinase.

J Biol Chem 14 — CAS PubMed Google Scholar Balkwill F Tumour necrosis factor and cancer. Nat Rev Cancer 9 5 — CAS PubMed Google Scholar Bechtel W, Bauer G Modulation of intercellular ROS signaling of human tumor cells. Anticancer Res 29 11 — CAS PubMed Google Scholar Bendayan M, Reddy JK Immunocytochemical localization of catalase and heat-labile enoyl-CoA hydratase in the livers of normal and peroxisome proliferator-treated rats.

Lab Invest 47 4 — CAS PubMed Google Scholar Beutler E Effect of flavin compounds on glutathione reductase activity: in vivo and in vitro studies. J Clin Invest 48 10 — CAS PubMed Central PubMed Google Scholar Brenneisen P, Sies H, Scharffetter-Kochanek K Ultraviolet-B irradiation and matrix metalloproteinases: from induction via signaling to initial events.

Ann N Y Acad Sci —43 CAS PubMed Google Scholar Brigelius-Flohe R Tissue-specific functions of individual glutathione peroxidases. Free Radic Biol Med 27 9—10 — CAS PubMed Google Scholar Brown NS, Bicknell R Hypoxia and oxidative stress in breast cancer.

Breast Cancer Res 3 5 — CAS PubMed Central PubMed Google Scholar Browne SE et al Treatment with a catalytic antioxidant corrects the neurobehavioral defect in ataxia-telangiectasia mice. Free Radic Biol Med 36 7 — CAS PubMed Google Scholar Burdon RH Superoxide and hydrogen peroxide in relation to mammalian cell proliferation.

Free Radic Biol Med 18 4 — CAS PubMed Google Scholar Burdon RH, Gill V, Rice-Evans C Oxidative stress and tumour cell proliferation. Free Radic Res Commun 11 1—3 —76 CAS PubMed Google Scholar Cadenas E Mitochondrial free radical production and cell signaling.

Mol Aspects Med 25 1—2 —26 CAS PubMed Google Scholar Chan DW et al Loss of MKP3 mediated by oxidative stress enhances tumorigenicity and chemoresistance of ovarian cancer cells.

Carcinogenesis 29 9 — CAS PubMed Google Scholar Cheng GC et al Oxidative stress and thioredoxin-interacting protein promote intravasation of melanoma cells. Exp Cell Res 2 — CAS PubMed Google Scholar Chiarugi P, Fiaschi T Redox signalling in anchorage-dependent cell growth.

Cell Signal 19 4 — CAS PubMed Google Scholar Chiu TT et al Protein kinase D2 mediates lysophosphatidic acid-induced interleukin 8 production in nontransformed human colonic epithelial cells through NF-kappaB.

Cancer Res 56 1 — CAS PubMed Google Scholar Coleman MC et al 2-deoxy-D-glucose causes cytotoxicity, oxidative stress, and radiosensitization in pancreatic cancer. Free Radic Biol Med 44 3 — CAS PubMed Google Scholar Cowell CF et al Loss of cell-cell contacts induces NF-kappaB via RhoA-mediated activation of protein kinase D1.

J Cell Biochem 4 — CAS PubMed Google Scholar Crompton M The mitochondrial permeability transition pore and its role in cell death. Biochem J Pt 2 — CAS PubMed Google Scholar Cui S et al Activated murine macrophages induce apoptosis in tumor cells through nitric oxide-dependent or -independent mechanisms.

Cancer Res 54 9 — CAS PubMed Google Scholar Cullen JJ et al The role of manganese superoxide dismutase in the growth of pancreatic adenocarcinoma. Cancer Res 63 6 — CAS PubMed Google Scholar Dang CV, Semenza GL Oncogenic alterations of metabolism.

Trends Biochem Sci 24 2 —72 CAS PubMed Google Scholar Dansen TB, Wirtz KW The peroxisome in oxidative stress. IUBMB Life 51 4 — CAS PubMed Google Scholar Dayal D et al Mitochondrial complex II dysfunction can contribute significantly to genomic instability after exposure to ionizing radiation.

Radiat Res 6 — CAS PubMed Central PubMed Google Scholar del Rio LA et al Metabolism of oxygen radicals in peroxisomes and cellular implications. Free Radic Biol Med 13 5 — PubMed Google Scholar Dewhirst MW, Cao Y, Moeller B Cycling hypoxia and free radicals regulate angiogenesis and radiotherapy response.

Nat Rev Cancer 8 6 — CAS PubMed Google Scholar Diaz B et al Tks5-dependent, nox-mediated generation of reactive oxygen species is necessary for invadopodia formation. Sci Signal 2 88 :ra53 PubMed Central PubMed Google Scholar Diehn M et al Association of reactive oxygen species levels and radioresistance in cancer stem cells.

Nature — CAS PubMed Central PubMed Google Scholar Ditch S, Paull TT The ATM protein kinase and cellular redox signaling: beyond the DNA damage response.

Trends Biochem Sci 37 1 —22 CAS PubMed Central PubMed Google Scholar Erler JT et al Lysyl oxidase is essential for hypoxia-induced metastasis.

Oncogene 24 31 — CAS PubMed Google Scholar Ferraro D et al Pro-metastatic signaling by c-Met through RAC-1 and reactive oxygen species ROS. Oncogene 25 26 — CAS PubMed Google Scholar Finkel T Redox-dependent signal transduction. FEBS Lett 1—2 —54 CAS PubMed Google Scholar Ganapathy V, Thangaraju M, Prasad PD Nutrient transporters in cancer: relevance to Warburg hypothesis and beyond.

Pharmacol Ther 1 —40 CAS PubMed Google Scholar Gardner HW Oxygen radical chemistry of polyunsaturated fatty acids. Free Radic Biol Med 7 1 —86 CAS PubMed Google Scholar Gianni D et al The involvement of the tyrosine kinase c-Src in the regulation of reactive oxygen species generation mediated by NADPH oxidase Mol Biol Cell 19 7 — CAS PubMed Central PubMed Google Scholar Gottlieb E, Vander Heiden MG, Thompson CB Bcl-x L prevents the initial decrease in mitochondrial membrane potential and subsequent reactive oxygen species production during tumor necrosis factor alpha-induced apoptosis.

Mol Cell Biol 20 15 — CAS PubMed Central PubMed Google Scholar Harris AL Hypoxia — a key regulatory factor in tumour growth.

Nat Rev Cancer 2 1 —47 CAS PubMed Google Scholar Hashimoto F, Hayashi H Significance of catalase in peroxisomal fatty acyl-CoA beta-oxidation: NADH oxidation by acetoacetyl-CoA and H 2 O 2. J Biochem 3 — CAS PubMed Google Scholar Higaki Y et al Oxidative stress stimulates skeletal muscle glucose uptake through a phosphatidylinositol 3-kinase-dependent pathway.

Am J Physiol Endocrinol Metab 5 :E—E CAS PubMed Central PubMed Google Scholar Hitchler MJ et al Epigenetic regulation of manganese superoxide dismutase expression in human breast cancer cells. Epigenetics 1 4 — PubMed Google Scholar Hitchler MJ, Oberley LW, Domann FE Epigenetic silencing of SOD2 by histone modifications in human breast cancer cells.

Free Radic Biol Med 45 11 — CAS PubMed Central PubMed Google Scholar Hockel M, Vaupel P Tumor hypoxia: definitions and current clinical, biologic, and molecular aspects. J Natl Cancer Inst 93 4 — CAS PubMed Google Scholar Hofmann B, Hecht HJ, Flohe L Peroxiredoxins.

Biol Chem 3—4 — CAS PubMed Google Scholar Hsu PP, Sabatini DM Cancer cell metabolism: Warburg and beyond. Cell 5 — CAS PubMed Google Scholar Huo YY et al PTEN deletion leads to deregulation of antioxidants and increased oxidative damage in mouse embryonic fibroblasts.

Free Radic Biol Med 44 8 — CAS PubMed Google Scholar Imbert V et al Tyrosine phosphorylation of I kappa B-alpha activates NF-kappa B without proteolytic degradation of I kappa B-alpha.

Cell 86 5 — CAS PubMed Google Scholar Irani K et al Mitogenic signaling mediated by oxidants in Ras-transformed fibroblasts. Science — CAS PubMed Google Scholar Jo M et al Oxidative stress is closely associated with tumor angiogenesis of hepatocellular carcinoma.

J Gastroenterol 46 6 — CAS PubMed Google Scholar Johnson TM et al Reactive oxygen species are downstream mediators of pdependent apoptosis. Proc Natl Acad Sci USA 93 21 — CAS PubMed Google Scholar Kaelin WG Jr, Ratcliffe PJ Oxygen sensing by metazoans: the central role of the HIF hydroxylase pathway.

Mol Cell 30 4 — CAS PubMed Google Scholar Keibel A, Singh V, Sharma MC Inflammation, microenvironment, and the immune system in cancer progression. Cell Cycle 6 23 — CAS PubMed Google Scholar Kheradmand F et al Role of Rac1 and oxygen radicals in collagenase-1 expression induced by cell shape change.

Science — CAS PubMed Google Scholar Kim JS, Huang TY, Bokoch GM Reactive oxygen species regulate a slingshot-cofilin activation pathway. Mol Biol Cell 20 11 — CAS PubMed Central PubMed Google Scholar Kumar B et al Oxidative stress is inherent in prostate cancer cells and is required for aggressive phenotype.

Cancer Res 68 6 — CAS PubMed Google Scholar Kundu N, Zhang S, Fulton AM Sublethal oxidative stress inhibits tumor cell adhesion and enhances experimental metastasis of murine mammary carcinoma. Clin Exp Metastasis 13 1 —22 CAS PubMed Google Scholar Lander HM et al A molecular redox switch on p21 ras.

J Biol Chem 7 — CAS PubMed Google Scholar Lauschke H et al Lipid peroxidation as additional marker in patients with colorectal cancer. Eur Surg Res 34 5 — CAS PubMed Google Scholar Lee SR et al Reversible inactivation of the tumor suppressor PTEN by H 2 O 2.

J Biol Chem 23 — CAS PubMed Google Scholar Lee WC et al Role of ERK in hydrogen peroxide-induced cell death of human glioma cells. Neurochem Res 30 2 — CAS PubMed Google Scholar Levine RL Carbonyl modified proteins in cellular regulation, aging, and disease.

Free Radic Biol Med 32 9 — CAS PubMed Google Scholar Li Q, Engelhardt JF Interleukin-1beta induction of NFkappaB is partially regulated by H 2 O 2 -mediated activation of NFkappaB-inducing kinase. J Biol Chem 3 — CAS PubMed Google Scholar Li N, Karin M Is NF-kappaB the sensor of oxidative stress?

FASEB J 13 10 — CAS PubMed Google Scholar Li D et al DNA adducts, genetic polymorphisms, and K-ras mutation in human pancreatic cancer.

Mutat Res 1—2 —48 CAS PubMed Google Scholar Liou GY, Storz P Reactive oxygen species in cancer. Free Radic Res 44 5 — CAS PubMed Google Scholar Litwin JA et al Immunocytochemical localization of peroxisomal enzymes in human liver biopsies. Am J Pathol 1 — CAS PubMed Google Scholar Liu LZ et al Reactive oxygen species regulate epidermal growth factor-induced vascular endothelial growth factor and hypoxia-inducible factor-1alpha expression through activation of AKT and P70S6K1 in human ovarian cancer cells.

Free Radic Biol Med 41 10 — CAS PubMed Google Scholar Lo YY, Cruz TF Involvement of reactive oxygen species in cytokine and growth factor induction of c-fos expression in chondrocytes. J Biol Chem 20 — CAS PubMed Google Scholar Lu T, Finkel T Free radicals and senescence.

Exp Cell Res 9 — CAS PubMed Central PubMed Google Scholar Maynard S et al Base excision repair of oxidative DNA damage and association with cancer and aging.

Biochim Biophys Acta 8 — CAS PubMed Central PubMed Google Scholar Meier B et al Human fibroblasts release reactive oxygen species in response to interleukin-1 or tumour necrosis factor-alpha. Biochem J 2 — CAS PubMed Google Scholar Meng TC, Fukada T, Tonks NK Reversible oxidation and inactivation of protein tyrosine phosphatases in vivo.

Mol Cell 9 2 — CAS PubMed Google Scholar Menon SG et al Differential susceptibility of nonmalignant human breast epithelial cells and breast cancer cells to thiol antioxidant-induced G 1 -delay. Cancer Res 64 24 — CAS PubMed Google Scholar Minamoto T, Mai M, Ronai Z K-ras mutation: early detection in molecular diagnosis and risk assessment of colorectal, pancreas, and lung cancers — a review.

Cancer Detect Prev 24 1 :1—12 CAS PubMed Google Scholar Minamoto T, Ougolkov AV, Mai M Detection of oncogenes in the diagnosis of cancers with active oncogenic signaling. Oncogene 25 26 — CAS PubMed Google Scholar Nakashima I et al Redox-linked signal transduction pathways for protein tyrosine kinase activation.

Antioxid Redox Signal 4 3 — CAS PubMed Google Scholar Nelson KK, Melendez JA Mitochondrial redox control of matrix metalloproteinases. Free Radic Biol Med 37 6 — CAS PubMed Google Scholar Neumann CA et al Essential role for the peroxiredoxin Prdx1 in erythrocyte antioxidant defence and tumour suppression.

Nature — CAS PubMed Google Scholar North JA, Spector AA, Buettner GR Cell fatty acid composition affects free radical formation during lipid peroxidation. Am J Physiol 1 Pt 1 :C—C CAS PubMed Google Scholar Ohba M et al Production of hydrogen peroxide by transforming growth factor-beta 1 and its involvement in induction of egr-1 in mouse osteoblastic cells.

J Cell Biol 4 — CAS PubMed Google Scholar Ostrakhovitch EA, Cherian MG Inhibition of extracellular signal regulated kinase ERK leads to apoptosis inducing factor AIF mediated apoptosis in epithelial breast cancer cells: the lack of effect of ERK in p53 mediated copper induced apoptosis.

J Cell Biochem 95 6 — CAS PubMed Google Scholar Pani G, Galeotti T Role of MnSOD and p66shc in mitochondrial response to p Antioxid Redox Signal 15 6 — CAS PubMed Google Scholar Pani G et al Redox-based escape mechanism from death: the cancer lesson. Antioxid Redox Signal 11 11 — CAS PubMed Google Scholar Parkash J, Felty Q, Roy D Estrogen exerts a spatial and temporal influence on reactive oxygen species generation that precedes calcium uptake in high-capacity mitochondria: implications for rapid nongenomic signaling of cell growth.

Biochemistry 45 9 — CAS PubMed Google Scholar Pastorino JG, Tafani M, Farber JL Tumor necrosis factor induces phosphorylation and translocation of BAD through a phosphatidylinositideOH kinase-dependent pathway. J Biol Chem 27 — CAS PubMed Google Scholar Pelicano H et al Mitochondrial dysfunction and reactive oxygen species imbalance promote breast cancer cell motility through a CXCLmediated mechanism.

Cancer Res 69 6 — CAS PubMed Central PubMed Google Scholar Pouyssegur J, Dayan F, Mazure NM Hypoxia signalling in cancer and approaches to enforce tumour regression.

Nature — CAS PubMed Google Scholar Prasad N et al Oxidative stress and vanadate induce tyrosine phosphorylation of phosphoinositide-dependent kinase 1 PDK1. Biochemistry 39 23 — CAS PubMed Google Scholar Qi XJ, Wildey GM, Howe PH Evidence that Ser87 of BimEL is phosphorylated by Akt and regulates BimEL apoptotic function.

J Biol Chem 2 — CAS PubMed Google Scholar Qian BZ, Pollard JW Macrophage diversity enhances tumor progression and metastasis. Free Radic Biol Med — CAS PubMed Central PubMed Google Scholar Radisky DC et al Rac1b and reactive oxygen species mediate MMPinduced EMT and genomic instability.

Nature — CAS PubMed Central PubMed Google Scholar Rajagopalan S et al Reactive oxygen species produced by macrophage-derived foam cells regulate the activity of vascular matrix metalloproteinases in vitro. Oncogene 18 49 — CAS PubMed Google Scholar Reichenbach J et al Elevated oxidative stress in patients with ataxia telangiectasia.

Antioxid Redox Signal 4 3 — CAS PubMed Google Scholar Rhee SG et al A family of novel peroxidases, peroxiredoxins. Biofactors 10 2—3 — CAS PubMed Google Scholar Rhee SG et al Hydrogen peroxide: a key messenger that modulates protein phosphorylation through cysteine oxidation. Sci STKE 53 :pe1 CAS PubMed Google Scholar Roberts PJ, Der CJ Targeting the Raf-MEK-ERK mitogen-activated protein kinase cascade for the treatment of cancer.

Oncogene 26 22 — CAS PubMed Google Scholar Rofstad EK et al Acidic extracellular pH promotes experimental metastasis of human melanoma cells in athymic nude mice. Cancer Res 66 13 — CAS PubMed Google Scholar Rozengurt E Protein kinase D signaling: multiple biological functions in health and disease.

Physiology Bethesda 26 1 —33 CAS Google Scholar Ruiz-Ramos R et al Sodium arsenite induces ROS generation, DNA oxidative damage, HO-1 and c-Myc proteins, NF-kappaB activation and cell proliferation in human breast cancer MCF-7 cells.

Mutat Res 1—2 — CAS PubMed Google Scholar Saitoh M et al Mammalian thioredoxin is a direct inhibitor of apoptosis signal-regulating kinase ASK 1.

EMBO J 17 9 — CAS PubMed Google Scholar Sarsour EH et al Manganese superoxide dismutase activity regulates transitions between quiescent and proliferative growth. Aging Cell 7 3 — CAS PubMed Central PubMed Google Scholar Schreck R, Albermann K, Baeuerle PA Nuclear factor kappa B: an oxidative stress-responsive transcription factor of eukaryotic cells a review.

Free Radic Res Commun 17 4 — CAS PubMed Google Scholar Senger DR et al Vascular permeability factor, tumor angiogenesis and stroma generation. Invasion Metastasis 14 1—6 — CAS PubMed Google Scholar Shackleton M et al Generation of a functional mammary gland from a single stem cell.

Nature —88 CAS PubMed Google Scholar Sharma R et al Antioxidant role of glutathione S-transferases: protection against oxidant toxicity and regulation of stress-mediated apoptosis. Mol Cells 24 1 — CAS PubMed Google Scholar Simon HU, Haj-Yehia A, Levi-Schaffer F Role of reactive oxygen species ROS in apoptosis induction.

Apoptosis 5 5 — CAS PubMed Google Scholar Singh I Mammalian peroxisomes: metabolism of oxygen and reactive oxygen species.

Ann N Y Acad Sci — CAS PubMed Google Scholar Song J et al PKD prevents H 2 O 2 -induced apoptosis via NF-kappaB and p38 MAPK in RIE-1 cells. Biochem Biophys Res Commun 3 — CAS PubMed Central PubMed Google Scholar Spitz DR et al Glucose deprivation-induced oxidative stress in human tumor cells.

Ann N Y Acad Sci — CAS PubMed Google Scholar Squier TC, Bigelow DJ Protein oxidation and age-dependent alterations in calcium homeostasis.

Front Biosci 5:D—D CAS PubMed Google Scholar Storz P Reactive oxygen species in tumor progression. Front Biosci — CAS PubMed Google Scholar Storz P Reactive oxygen species-mediated mitochondria-to-nucleus signaling: a key to aging and radical-caused diseases.

Sci STKE :re3 PubMed Google Scholar Storz P Mitochondrial ROS—radical detoxification, mediated by protein kinase D. Trends Cell Biol 17 1 —18 CAS PubMed Google Scholar Storz P Forkhead homeobox type O transcription factors in the responses to oxidative stress.

Antioxid Redox Signal 14 4 — CAS PubMed Google Scholar Storz P, Toker A Protein kinase D mediates a stress-induced NF-kappaB activation and survival pathway. EMBO J 22 1 — CAS PubMed Google Scholar Storz P, Doppler H, Toker A a Protein kinase Cdelta selectively regulates protein kinase D-dependent activation of NF-kappaB in oxidative stress signaling.

Mol Cell Biol 24 7 — CAS PubMed Central PubMed Google Scholar Storz P, Doppler H, Toker A b Activation loop phosphorylation controls protein kinase D-dependent activation of nuclear factor kappaB. Mol Pharmacol 66 4 — CAS PubMed Google Scholar Storz P, Doppler H, Toker A a Protein kinase D mediates mitochondrion-to-nucleus signaling and detoxification from mitochondrial reactive oxygen species.

Mol Cell Biol 25 19 — CAS PubMed Central PubMed Google Scholar Storz P et al b Functional dichotomy of A20 in apoptotic and necrotic cell death. Biochem J Pt 1 —55 CAS PubMed Google Scholar Storz P et al FOXO3a promotes tumor cell invasion through the induction of matrix metalloproteinases.

Mol Cell Biol 29 18 — CAS PubMed Central PubMed Google Scholar Sun G, Kemble DJ To C or not to C: direct and indirect redox regulation of Src protein tyrosine kinase.

Cell Cycle 8 15 — CAS PubMed Google Scholar Sundaresan M et al Requirement for generation of H 2 O 2 for platelet-derived growth factor signal transduction. Science — CAS PubMed Google Scholar Sundaresan M et al Regulation of reactive-oxygen-species generation in fibroblasts by Rac1.

Biochem J Pt 2 — CAS PubMed Google Scholar Szatrowski TP, Nathan CF Production of large amounts of hydrogen peroxide by human tumor cells.

Cancer Res 51 3 — CAS PubMed Google Scholar Takeda K et al Roles of MAPKKK ASK1 in stress-induced cell death. Cell Struct Funct 28 1 —29 CAS PubMed Google Scholar Tanno T, Matsui W Development and maintenance of cancer stem cells under chronic inflammation. J Nippon Med Sch 78 3 — CAS PubMed Central PubMed Google Scholar Tiku ML, Liesch JB, Robertson FM Production of hydrogen peroxide by rabbit articular chondrocytes.

J Immunol 2 — CAS PubMed Google Scholar Tobar N et al RAC1 activity and intracellular ROS modulate the migratory potential of MCF-7 cells through a NADPH oxidase and NFkappaB-dependent mechanism.

Cancer Lett 1 — CAS PubMed Google Scholar Tothova Z et al FoxOs are critical mediators of hematopoietic stem cell resistance to physiologic oxidative stress.

Cell 2 — CAS PubMed Google Scholar Townsend DM, Tew KD The role of glutathione-S-transferase in anti-cancer drug resistance.

Oncogene 22 47 — CAS PubMed Google Scholar Trachootham D et al Selective killing of oncogenically transformed cells through a ROS-mediated mechanism by beta-phenylethyl isothiocyanate.

Cancer Cell 10 3 — CAS PubMed Google Scholar Trachootham D, Alexandre J, Huang P Targeting cancer cells by ROS-mediated mechanisms: a radical therapeutic approach?

Nat Rev Drug Discov 8 7 — CAS PubMed Google Scholar van Wetering S et al Reactive oxygen species mediate Rac-induced loss of cell-cell adhesion in primary human endothelial cells. J Cell Sci Pt 9 — PubMed Google Scholar Wang M et al Manganese superoxide dismutase suppresses hypoxic induction of hypoxia-inducible factor-1alpha and vascular endothelial growth factor.

Oncogene 24 55 — CAS PubMed Google Scholar Wang Y et al The endogenous reactive oxygen species promote NF-kappaB activation by targeting on activation of NF-kappaB-inducing kinase in oral squamous carcinoma cells. Free Radic Res 41 9 — CAS PubMed Google Scholar Ward JF Biochemistry of DNA lesions.

Radiat Res Suppl 8:S—S CAS PubMed Google Scholar Wells-Knecht MC et al Age-dependent increase in ortho-tyrosine and methionine sulfoxide in human skin collagen is not accelerated in diabetes.

J Clin Invest 4 — CAS PubMed Central PubMed Google Scholar Wenk J et al Stable overexpression of manganese superoxide dismutase in mitochondria identifies hydrogen peroxide as a major oxidant in the APmediated induction of matrix-degrading metalloprotease J Biol Chem 36 — CAS PubMed Google Scholar Werner E, Werb Z Integrins engage mitochondrial function for signal transduction by a mechanism dependent on Rho GTPases.

J Cell Biol 2 — CAS PubMed Google Scholar Wiseman H, Halliwell B Damage to DNA by reactive oxygen and nitrogen species: role in inflammatory disease and progression to cancer. Biochem J Pt 1 —29 CAS PubMed Google Scholar Wood ZA et al Structure, mechanism and regulation of peroxiredoxins.

Trends Biochem Sci 28 1 —40 CAS PubMed Google Scholar Wu WS The signaling mechanism of ROS in tumor progression. Cancer Metastasis Rev 25 4 — CAS PubMed Google Scholar Xia C et al Reactive oxygen species regulate angiogenesis and tumor growth through vascular endothelial growth factor.

Cancer Res 67 22 — CAS PubMed Google Scholar Xin M, Deng X Nicotine inactivation of the proapoptotic function of Bax through phosphorylation.

J Biol Chem 11 — CAS PubMed Google Scholar Xu YC et al Involvement of TRAF4 in oxidative activation of c-Jun N-terminal kinase. Cell Cycle 5 6 — PubMed Google Scholar Yoeli-Lerner M et al Akt blocks breast cancer cell motility and invasion through the transcription factor NFAT.

Mol Cell 20 4 — CAS PubMed Google Scholar Zhang R et al In vitro and in vivo induction of apoptosis by capsaicin in pancreatic cancer cells is mediated through ROS generation and mitochondrial death pathway.

Apoptosis 13 12 — CAS PubMed Google Scholar Download references. Acknowledgements The author would like to thank Heike Döppler and Jenni Bachhofer for critical reading of the manuscript. Author information Authors and Affiliations Department of Cancer Biology, Mayo Clinic, San Pablo Road, Jacksonville, FL, , USA Peter Storz Authors Peter Storz View author publications.

Editor information Editors and Affiliations Mol. and Developmental Biology, University of Michigan, Ann Arbor, Michigan, USA Ursula Jakob The Alexander Silberman Institute of Life Science, Department of Biological Chemistry, The Hebrew University of Jerusalem, Jerusalem, Israel Dana Reichmann.

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J Biol Chem 20 — Lu T, Finkel T Free radicals and senescence. Exp Cell Res 9 — Maynard S et al Base excision repair of oxidative DNA damage and association with cancer and aging. Carcinogenesis 30 1 :2— Biochim Biophys Acta 8 — Meier B et al Human fibroblasts release reactive oxygen species in response to interleukin-1 or tumour necrosis factor-alpha.

Biochem J 2 — Meng TC, Fukada T, Tonks NK Reversible oxidation and inactivation of protein tyrosine phosphatases in vivo. Mol Cell 9 2 — Menon SG et al Differential susceptibility of nonmalignant human breast epithelial cells and breast cancer cells to thiol antioxidant-induced G 1 -delay.

Antioxid Redox Signal 7 5—6 — Cancer Res 64 24 — Minamoto T, Mai M, Ronai Z K-ras mutation: early detection in molecular diagnosis and risk assessment of colorectal, pancreas, and lung cancers — a review. Cancer Detect Prev 24 1 :1— Minamoto T, Ougolkov AV, Mai M Detection of oncogenes in the diagnosis of cancers with active oncogenic signaling.

Expert Rev Mol Diagn 2 6 — Nakashima I et al Redox-linked signal transduction pathways for protein tyrosine kinase activation. Antioxid Redox Signal 4 3 — Nelson KK, Melendez JA Mitochondrial redox control of matrix metalloproteinases.

Free Radic Biol Med 37 6 — Neumann CA et al Essential role for the peroxiredoxin Prdx1 in erythrocyte antioxidant defence and tumour suppression. North JA, Spector AA, Buettner GR Cell fatty acid composition affects free radical formation during lipid peroxidation. Am J Physiol 1 Pt 1 :C—C Ohba M et al Production of hydrogen peroxide by transforming growth factor-beta 1 and its involvement in induction of egr-1 in mouse osteoblastic cells.

J Cell Biol 4 — Ostrakhovitch EA, Cherian MG Inhibition of extracellular signal regulated kinase ERK leads to apoptosis inducing factor AIF mediated apoptosis in epithelial breast cancer cells: the lack of effect of ERK in p53 mediated copper induced apoptosis.

J Cell Biochem 95 6 — Pani G, Galeotti T Role of MnSOD and p66shc in mitochondrial response to p Antioxid Redox Signal 15 6 — Pani G et al Redox-based escape mechanism from death: the cancer lesson. Antioxid Redox Signal 11 11 — Parkash J, Felty Q, Roy D Estrogen exerts a spatial and temporal influence on reactive oxygen species generation that precedes calcium uptake in high-capacity mitochondria: implications for rapid nongenomic signaling of cell growth.

Biochemistry 45 9 — Pastorino JG, Tafani M, Farber JL Tumor necrosis factor induces phosphorylation and translocation of BAD through a phosphatidylinositideOH kinase-dependent pathway. J Biol Chem 27 — Pelicano H et al Mitochondrial dysfunction and reactive oxygen species imbalance promote breast cancer cell motility through a CXCLmediated mechanism.

Cancer Res 69 6 — Pouyssegur J, Dayan F, Mazure NM Hypoxia signalling in cancer and approaches to enforce tumour regression.

Prasad N et al Oxidative stress and vanadate induce tyrosine phosphorylation of phosphoinositide-dependent kinase 1 PDK1. Biochemistry 39 23 — Qi XJ, Wildey GM, Howe PH Evidence that Ser87 of BimEL is phosphorylated by Akt and regulates BimEL apoptotic function.

J Biol Chem 2 — Qian BZ, Pollard JW Macrophage diversity enhances tumor progression and metastasis. Cell 1 — Free Radic Biol Med — Radisky DC et al Rac1b and reactive oxygen species mediate MMPinduced EMT and genomic instability. Rajagopalan S et al Reactive oxygen species produced by macrophage-derived foam cells regulate the activity of vascular matrix metalloproteinases in vitro.

Implications for atherosclerotic plaque stability. J Clin Invest 98 11 — Oncogene 18 49 — Reichenbach J et al Elevated oxidative stress in patients with ataxia telangiectasia. Rhee SG et al A family of novel peroxidases, peroxiredoxins.

Biofactors 10 2—3 — Rhee SG et al Hydrogen peroxide: a key messenger that modulates protein phosphorylation through cysteine oxidation. Sci STKE 53 :pe1. Roberts PJ, Der CJ Targeting the Raf-MEK-ERK mitogen-activated protein kinase cascade for the treatment of cancer.

Oncogene 26 22 — Rofstad EK et al Acidic extracellular pH promotes experimental metastasis of human melanoma cells in athymic nude mice. Cancer Res 66 13 — Rozengurt E Protein kinase D signaling: multiple biological functions in health and disease. Physiology Bethesda 26 1 — CAS Google Scholar.

Ruiz-Ramos R et al Sodium arsenite induces ROS generation, DNA oxidative damage, HO-1 and c-Myc proteins, NF-kappaB activation and cell proliferation in human breast cancer MCF-7 cells. Saitoh M et al Mammalian thioredoxin is a direct inhibitor of apoptosis signal-regulating kinase ASK 1. EMBO J 17 9 — Sarsour EH et al Manganese superoxide dismutase activity regulates transitions between quiescent and proliferative growth.

Aging Cell 7 3 — Schreck R, Albermann K, Baeuerle PA Nuclear factor kappa B: an oxidative stress-responsive transcription factor of eukaryotic cells a review. Free Radic Res Commun 17 4 — Senger DR et al Vascular permeability factor, tumor angiogenesis and stroma generation.

Invasion Metastasis 14 1—6 — Shackleton M et al Generation of a functional mammary gland from a single stem cell. Sharma R et al Antioxidant role of glutathione S-transferases: protection against oxidant toxicity and regulation of stress-mediated apoptosis.

Antioxid Redox Signal 6 2 — Mol Cells 24 1 — Simon HU, Haj-Yehia A, Levi-Schaffer F Role of reactive oxygen species ROS in apoptosis induction. Apoptosis 5 5 — Singh I Mammalian peroxisomes: metabolism of oxygen and reactive oxygen species. Song J et al PKD prevents H 2 O 2 -induced apoptosis via NF-kappaB and p38 MAPK in RIE-1 cells.

Biochem Biophys Res Commun 3 — Spitz DR et al Glucose deprivation-induced oxidative stress in human tumor cells. A fundamental defect in metabolism?

Squier TC, Bigelow DJ Protein oxidation and age-dependent alterations in calcium homeostasis. Front Biosci 5:D—D Storz P Reactive oxygen species in tumor progression. Front Biosci — Storz P Reactive oxygen species-mediated mitochondria-to-nucleus signaling: a key to aging and radical-caused diseases.

Sci STKE :re3. Storz P Mitochondrial ROS—radical detoxification, mediated by protein kinase D. Trends Cell Biol 17 1 — Storz P Forkhead homeobox type O transcription factors in the responses to oxidative stress.

Antioxid Redox Signal 14 4 — Storz P, Toker A Protein kinase D mediates a stress-induced NF-kappaB activation and survival pathway.

EMBO J 22 1 — Storz P, Doppler H, Toker A a Protein kinase Cdelta selectively regulates protein kinase D-dependent activation of NF-kappaB in oxidative stress signaling.

Mol Cell Biol 24 7 — Storz P, Doppler H, Toker A b Activation loop phosphorylation controls protein kinase D-dependent activation of nuclear factor kappaB. Mol Pharmacol 66 4 — Storz P, Doppler H, Toker A a Protein kinase D mediates mitochondrion-to-nucleus signaling and detoxification from mitochondrial reactive oxygen species.

Mol Cell Biol 25 19 — Storz P et al b Functional dichotomy of A20 in apoptotic and necrotic cell death. Biochem J Pt 1 — Storz P et al FOXO3a promotes tumor cell invasion through the induction of matrix metalloproteinases.

Mol Cell Biol 29 18 — Sun G, Kemble DJ To C or not to C: direct and indirect redox regulation of Src protein tyrosine kinase. Cell Cycle 8 15 — Sundaresan M et al Requirement for generation of H 2 O 2 for platelet-derived growth factor signal transduction.

Sundaresan M et al Regulation of reactive-oxygen-species generation in fibroblasts by Rac1. Szatrowski TP, Nathan CF Production of large amounts of hydrogen peroxide by human tumor cells. Cancer Res 51 3 — Takeda K et al Roles of MAPKKK ASK1 in stress-induced cell death. Cell Struct Funct 28 1 — Tanno T, Matsui W Development and maintenance of cancer stem cells under chronic inflammation.

J Nippon Med Sch 78 3 — Tiku ML, Liesch JB, Robertson FM Production of hydrogen peroxide by rabbit articular chondrocytes.

Enhancement by cytokines. J Immunol 2 — Tobar N et al RAC1 activity and intracellular ROS modulate the migratory potential of MCF-7 cells through a NADPH oxidase and NFkappaB-dependent mechanism.

Cancer Lett 1 — Tothova Z et al FoxOs are critical mediators of hematopoietic stem cell resistance to physiologic oxidative stress. Cell 2 — Townsend DM, Tew KD The role of glutathione-S-transferase in anti-cancer drug resistance.

Oncogene 22 47 — Trachootham D et al Selective killing of oncogenically transformed cells through a ROS-mediated mechanism by beta-phenylethyl isothiocyanate. Cancer Cell 10 3 — Trachootham D, Alexandre J, Huang P Targeting cancer cells by ROS-mediated mechanisms: a radical therapeutic approach?

Nat Rev Drug Discov 8 7 — van Wetering S et al Reactive oxygen species mediate Rac-induced loss of cell-cell adhesion in primary human endothelial cells. J Cell Sci Pt 9 — Wang M et al Manganese superoxide dismutase suppresses hypoxic induction of hypoxia-inducible factor-1alpha and vascular endothelial growth factor.

Oncogene 24 55 — Wang Y et al The endogenous reactive oxygen species promote NF-kappaB activation by targeting on activation of NF-kappaB-inducing kinase in oral squamous carcinoma cells. Free Radic Res 41 9 — Ward JF Biochemistry of DNA lesions. Radiat Res Suppl 8:S—S Wells-Knecht MC et al Age-dependent increase in ortho-tyrosine and methionine sulfoxide in human skin collagen is not accelerated in diabetes.

Evidence against a generalized increase in oxidative stress in diabetes. J Clin Invest 4 — Wenk J et al Stable overexpression of manganese superoxide dismutase in mitochondria identifies hydrogen peroxide as a major oxidant in the APmediated induction of matrix-degrading metalloprotease J Biol Chem 36 — Werner E, Werb Z Integrins engage mitochondrial function for signal transduction by a mechanism dependent on Rho GTPases.

J Cell Biol 2 — Wiseman H, Halliwell B Damage to DNA by reactive oxygen and nitrogen species: role in inflammatory disease and progression to cancer. Wood ZA et al Structure, mechanism and regulation of peroxiredoxins. Trends Biochem Sci 28 1 — Wu WS The signaling mechanism of ROS in tumor progression.

Cancer Metastasis Rev 25 4 — Xia C et al Reactive oxygen species regulate angiogenesis and tumor growth through vascular endothelial growth factor. Cancer Res 67 22 — Xin M, Deng X Nicotine inactivation of the proapoptotic function of Bax through phosphorylation.

J Biol Chem 11 — Xu YC et al Involvement of TRAF4 in oxidative activation of c-Jun N-terminal kinase. J Biol Chem 31 — Cell Cycle 5 6 — Yoeli-Lerner M et al Akt blocks breast cancer cell motility and invasion through the transcription factor NFAT.

Mol Cell 20 4 — Zhang R et al In vitro and in vivo induction of apoptosis by capsaicin in pancreatic cancer cells is mediated through ROS generation and mitochondrial death pathway. Apoptosis 13 12 — Download references. The author would like to thank Heike Döppler and Jenni Bachhofer for critical reading of the manuscript.

Work in the Storz laboratory is supported by the NIH grants GM and CA Department of Cancer Biology, Mayo Clinic, San Pablo Road, Jacksonville, FL, , USA. You can also search for this author in PubMed Google Scholar. Correspondence to Peter Storz. and Developmental Biology, University of Michigan, Ann Arbor, Michigan, USA.

The Alexander Silberman Institute of Life Science, Department of Biological Chemistry, The Hebrew University of Jerusalem, Jerusalem, Israel. Reprints and permissions. Storz, P. Oxidative Stress in Cancer. In: Jakob, U. eds Oxidative Stress and Redox Regulation.

Springer, Dordrecht. Published : 14 February Publisher Name : Springer, Dordrecht. Print ISBN : Online ISBN : eBook Packages : Biomedical and Life Sciences Biomedical and Life Sciences R0.

Anyone you share the following link with will be able to read this content:. Sorry, a shareable link is not currently available for this article. Provided by the Springer Nature SharedIt content-sharing initiative. Policies and ethics. Skip to main content. Abstract Increased oxidative stress is a common feature observed in many different types of cancer.

Keywords Oxidative stress Reactive oxygen species Antioxidants Tumor Cancer. Buying options Chapter EUR eBook EUR Softcover Book EUR Hardcover Book EUR Tax calculation will be finalised at checkout Purchases are for personal use only Learn about institutional subscriptions.

References Ahmed KM, Cao N, Li JJ HER-2 and NF-kappaB as the targets for therapy-resistant breast cancer. Anticancer Res 26 6B — CAS PubMed Central PubMed Google Scholar Aykin-Burns N et al Increased levels of superoxide and H 2 O 2 mediate the differential susceptibility of cancer cells versus normal cells to glucose deprivation.

Biochem J 1 —37 CAS PubMed Central PubMed Google Scholar Babior BM NADPH oxidase: an update. Blood 93 5 — CAS PubMed Google Scholar Bae YS et al Platelet-derived growth factor-induced H 2 O 2 production requires the activation of phosphatidylinositol 3-kinase.

J Biol Chem 14 — CAS PubMed Google Scholar Balkwill F Tumour necrosis factor and cancer. Nat Rev Cancer 9 5 — CAS PubMed Google Scholar Bechtel W, Bauer G Modulation of intercellular ROS signaling of human tumor cells.

Anticancer Res 29 11 — CAS PubMed Google Scholar Bendayan M, Reddy JK Immunocytochemical localization of catalase and heat-labile enoyl-CoA hydratase in the livers of normal and peroxisome proliferator-treated rats.

Lab Invest 47 4 — CAS PubMed Google Scholar Beutler E Effect of flavin compounds on glutathione reductase activity: in vivo and in vitro studies. J Clin Invest 48 10 — CAS PubMed Central PubMed Google Scholar Brenneisen P, Sies H, Scharffetter-Kochanek K Ultraviolet-B irradiation and matrix metalloproteinases: from induction via signaling to initial events.

Ann N Y Acad Sci —43 CAS PubMed Google Scholar Brigelius-Flohe R Tissue-specific functions of individual glutathione peroxidases. Free Radic Biol Med 27 9—10 — CAS PubMed Google Scholar Brown NS, Bicknell R Hypoxia and oxidative stress in breast cancer.

Breast Cancer Res 3 5 — CAS PubMed Central PubMed Google Scholar Browne SE et al Treatment with a catalytic antioxidant corrects the neurobehavioral defect in ataxia-telangiectasia mice.

Free Radic Biol Med 36 7 — CAS PubMed Google Scholar Burdon RH Superoxide and hydrogen peroxide in relation to mammalian cell proliferation. Free Radic Biol Med 18 4 — CAS PubMed Google Scholar Burdon RH, Gill V, Rice-Evans C Oxidative stress and tumour cell proliferation. Free Radic Res Commun 11 1—3 —76 CAS PubMed Google Scholar Cadenas E Mitochondrial free radical production and cell signaling.

Mol Aspects Med 25 1—2 —26 CAS PubMed Google Scholar Chan DW et al Loss of MKP3 mediated by oxidative stress enhances tumorigenicity and chemoresistance of ovarian cancer cells.

Carcinogenesis 29 9 — CAS PubMed Google Scholar Cheng GC et al Oxidative stress and thioredoxin-interacting protein promote intravasation of melanoma cells. Exp Cell Res 2 — CAS PubMed Google Scholar Chiarugi P, Fiaschi T Redox signalling in anchorage-dependent cell growth.

Cell Signal 19 4 — CAS PubMed Google Scholar Chiu TT et al Protein kinase D2 mediates lysophosphatidic acid-induced interleukin 8 production in nontransformed human colonic epithelial cells through NF-kappaB.

Cancer Res 56 1 — CAS PubMed Google Scholar Coleman MC et al 2-deoxy-D-glucose causes cytotoxicity, oxidative stress, and radiosensitization in pancreatic cancer.

Free Radic Biol Med 44 3 — CAS PubMed Google Scholar Cowell CF et al Loss of cell-cell contacts induces NF-kappaB via RhoA-mediated activation of protein kinase D1.

J Cell Biochem 4 — CAS PubMed Google Scholar Crompton M The mitochondrial permeability transition pore and its role in cell death. Biochem J Pt 2 — CAS PubMed Google Scholar Cui S et al Activated murine macrophages induce apoptosis in tumor cells through nitric oxide-dependent or -independent mechanisms.

Cancer Res 54 9 — CAS PubMed Google Scholar Cullen JJ et al The role of manganese superoxide dismutase in the growth of pancreatic adenocarcinoma. Cancer Res 63 6 — CAS PubMed Google Scholar Dang CV, Semenza GL Oncogenic alterations of metabolism.

Trends Biochem Sci 24 2 —72 CAS PubMed Google Scholar Dansen TB, Wirtz KW The peroxisome in oxidative stress. IUBMB Life 51 4 — CAS PubMed Google Scholar Dayal D et al Mitochondrial complex II dysfunction can contribute significantly to genomic instability after exposure to ionizing radiation. Radiat Res 6 — CAS PubMed Central PubMed Google Scholar del Rio LA et al Metabolism of oxygen radicals in peroxisomes and cellular implications.

Free Radic Biol Med 13 5 — PubMed Google Scholar Dewhirst MW, Cao Y, Moeller B Cycling hypoxia and free radicals regulate angiogenesis and radiotherapy response. Nat Rev Cancer 8 6 — CAS PubMed Google Scholar Diaz B et al Tks5-dependent, nox-mediated generation of reactive oxygen species is necessary for invadopodia formation.

Sci Signal 2 88 :ra53 PubMed Central PubMed Google Scholar Diehn M et al Association of reactive oxygen species levels and radioresistance in cancer stem cells. Nature — CAS PubMed Central PubMed Google Scholar Ditch S, Paull TT The ATM protein kinase and cellular redox signaling: beyond the DNA damage response.

Trends Biochem Sci 37 1 —22 CAS PubMed Central PubMed Google Scholar Erler JT et al Lysyl oxidase is essential for hypoxia-induced metastasis. Oncogene 24 31 — CAS PubMed Google Scholar Ferraro D et al Pro-metastatic signaling by c-Met through RAC-1 and reactive oxygen species ROS.

Oncogene 25 26 — CAS PubMed Google Scholar Finkel T Redox-dependent signal transduction. FEBS Lett 1—2 —54 CAS PubMed Google Scholar Ganapathy V, Thangaraju M, Prasad PD Nutrient transporters in cancer: relevance to Warburg hypothesis and beyond. Pharmacol Ther 1 —40 CAS PubMed Google Scholar Gardner HW Oxygen radical chemistry of polyunsaturated fatty acids.

Free Radic Biol Med 7 1 —86 CAS PubMed Google Scholar Gianni D et al The involvement of the tyrosine kinase c-Src in the regulation of reactive oxygen species generation mediated by NADPH oxidase Mol Biol Cell 19 7 — CAS PubMed Central PubMed Google Scholar Gottlieb E, Vander Heiden MG, Thompson CB Bcl-x L prevents the initial decrease in mitochondrial membrane potential and subsequent reactive oxygen species production during tumor necrosis factor alpha-induced apoptosis.

Mol Cell Biol 20 15 — CAS PubMed Central PubMed Google Scholar Harris AL Hypoxia — a key regulatory factor in tumour growth. Nat Rev Cancer 2 1 —47 CAS PubMed Google Scholar Hashimoto F, Hayashi H Significance of catalase in peroxisomal fatty acyl-CoA beta-oxidation: NADH oxidation by acetoacetyl-CoA and H 2 O 2.

J Biochem 3 — CAS PubMed Google Scholar Higaki Y et al Oxidative stress stimulates skeletal muscle glucose uptake through a phosphatidylinositol 3-kinase-dependent pathway. Am J Physiol Endocrinol Metab 5 :E—E CAS PubMed Central PubMed Google Scholar Hitchler MJ et al Epigenetic regulation of manganese superoxide dismutase expression in human breast cancer cells.

Epigenetics 1 4 — PubMed Google Scholar Hitchler MJ, Oberley LW, Domann FE Epigenetic silencing of SOD2 by histone modifications in human breast cancer cells. Free Radic Biol Med 45 11 — CAS PubMed Central PubMed Google Scholar Hockel M, Vaupel P Tumor hypoxia: definitions and current clinical, biologic, and molecular aspects.

J Natl Cancer Inst 93 4 — CAS PubMed Google Scholar Hofmann B, Hecht HJ, Flohe L Peroxiredoxins. Biol Chem 3—4 — CAS PubMed Google Scholar Hsu PP, Sabatini DM Cancer cell metabolism: Warburg and beyond. Cell 5 — CAS PubMed Google Scholar Huo YY et al PTEN deletion leads to deregulation of antioxidants and increased oxidative damage in mouse embryonic fibroblasts.

Free Radic Biol Med 44 8 — CAS PubMed Google Scholar Imbert V et al Tyrosine phosphorylation of I kappa B-alpha activates NF-kappa B without proteolytic degradation of I kappa B-alpha.

Cell 86 5 — CAS PubMed Google Scholar Irani K et al Mitogenic signaling mediated by oxidants in Ras-transformed fibroblasts. Science — CAS PubMed Google Scholar Jo M et al Oxidative stress is closely associated with tumor angiogenesis of hepatocellular carcinoma.

J Gastroenterol 46 6 — CAS PubMed Google Scholar Johnson TM et al Reactive oxygen species are downstream mediators of pdependent apoptosis. Proc Natl Acad Sci USA 93 21 — CAS PubMed Google Scholar Kaelin WG Jr, Ratcliffe PJ Oxygen sensing by metazoans: the central role of the HIF hydroxylase pathway.

Mol Cell 30 4 — CAS PubMed Google Scholar Keibel A, Singh V, Sharma MC Inflammation, microenvironment, and the immune system in cancer progression. Cell Cycle 6 23 — CAS PubMed Google Scholar Kheradmand F et al Role of Rac1 and oxygen radicals in collagenase-1 expression induced by cell shape change.

Science — CAS PubMed Google Scholar Kim JS, Huang TY, Bokoch GM Reactive oxygen species regulate a slingshot-cofilin activation pathway.

Mol Biol Cell 20 11 — CAS PubMed Central PubMed Google Scholar Kumar B et al Oxidative stress is inherent in prostate cancer cells and is required for aggressive phenotype. Cancer Res 68 6 — CAS PubMed Google Scholar Kundu N, Zhang S, Fulton AM Sublethal oxidative stress inhibits tumor cell adhesion and enhances experimental metastasis of murine mammary carcinoma.

Clin Exp Metastasis 13 1 —22 CAS PubMed Google Scholar Lander HM et al A molecular redox switch on p21 ras. J Biol Chem 7 — CAS PubMed Google Scholar Lauschke H et al Lipid peroxidation as additional marker in patients with colorectal cancer. Eur Surg Res 34 5 — CAS PubMed Google Scholar Lee SR et al Reversible inactivation of the tumor suppressor PTEN by H 2 O 2.

J Biol Chem 23 — CAS PubMed Google Scholar Lee WC et al Role of ERK in hydrogen peroxide-induced cell death of human glioma cells. Pathak C, Vinayak M Modulation of lactate dehydrogenase isozymes by modified base queuine. Mol Biol Rep — Mohammad GH, Damink SO, Malago M, Dhar DK, Pereira SP Pyruvate kinase M2 and lactate dehydrogenase A are overexpressed in pancreatic cancer and correlate with poor outcome.

PLoS One e Hsu M-C, Hung W-C Pyruvate kinase M2 fuels multiple aspects of cancer cells: from cellular metabolism, transcriptional regulation to extracellular signaling. Mol Cancer Gui DY, Lewis CA, Vander Heiden MG Allosteric regulation of PKM2 allows cellular adaptation to different physiological states.

Sci Signal 6:pe7. Anastasiou D, Yu Y, Israelsen WJ, Jiang J-K, Boxer MB, Hong BS, Tempel W, Dimov S, Shen M, Jha A Pyruvate kinase M2 activators promote tetramer formation and suppress tumorigenesis.

Nat Chem Biol Anastasiou D, Poulogiannis G, Asara JM, Boxer MB, Jiang J-K, Shen M, Bellinger G, Sasaki AT, Locasale JW, Auld DSJS Inhibition of pyruvate kinase M2 by reactive oxygen species contributes to cellular antioxidant responses.

Science — Finley LW, Carracedo A, Lee J, Souza A, Egia A, Zhang J, Teruya-Feldstein J, Moreira PI, Cardoso SM, Clish CB SIRT3 opposes reprogramming of cancer cell metabolism through HIF1α destabilization.

Fiaschi T, Chiarugi P Oxidative stress, tumor microenvironment, and metabolic reprogramming: a diabolic liaison. Int J Cell Biol Burdon RH, Gill V, Rice-Evans C Oxidative stress and tumour cell proliferation.

Free Radic Res Commun — Kumari S, Badana AK, Malla R Reactive oxygen species: a key constituent in cancer survival. Biomark Insights Storz P Reactive oxygen species in tumor progression. Front Biosci — Yang Y, Fang E, Luo J, Wu H, Jiang Y, Liu Y, Tong S, Wang Z, Zhou R, Tong Q The antioxidant alpha-lipoic acid inhibits proliferation and invasion of human gastric cancer cells via suppression of STAT3-mediated MUC4 gene expression.

Hamanaka RB, Chandel NS Mitochondrial reactive oxygen species regulate cellular signaling and dictate biological outcomes. Wang M, Kirk JS, Venkataraman S, Domann FE, Zhang HJ, Schafer FQ, Flanagan SW, Weydert CJ, Spitz DR, Buettner GR Manganese superoxide dismutase suppresses hypoxic induction of hypoxia-inducible factor-1 α and vascular endothelial growth factor.

Oncogene — Patterson JC, Joughin BA, van de Kooij B, Lim DC, Lauffenburger DA, Yaffe MB ROS and oxidative stress are elevated in mitosis during asynchronous cell cycle progression and are exacerbated by mitotic arrest. Cell Syst — Ranjan P, Anathy V, Burch PM, Weirather K, Lambeth JD, Heintz NH Redox-dependent expression of cyclin D1 and cell proliferation by Nox1 in mouse lung epithelial cells.

Exp Cell Res — Verbon EH, Post JA, Boonstra J The influence of reactive oxygen species on cell cycle progression in mammalian cells. Gene —6. Kelkel M, Schumacher M, Dicato M, Diederich M Antioxidant and anti-proliferative properties of lycopene.

Laphanuwat P, Likasitwatanakul P, Sittithumcharee G, Thaphaengphan A, Chomanee N, Suppramote O, Ketaroonrut N, Charngkaew K, Lam EW-F, Okada S Cyclin D1 depletion interferes with oxidative balance and promotes cancer cell senescence. J Cell Sci — Nutr J Kozlov SV, Waardenberg AJ, Engholm-Keller K, Arthur JW, Graham ME, Lavin M Reactive oxygen species ROS -activated ATM-dependent phosphorylation of cytoplasmic substrates identified by large-scale phosphoproteomics screen.

Mol Cell Proteomics — Mantovani F, Collavin L, Del Sal G Mutant p53 as a guardian of the cancer cell. Cell Death Differ — Ma Q Role of nrf2 in oxidative stress and toxicity. Annu Rev Pharmacol Toxicol — Haupt S, Raghu D, Haupt Y Mutant p53 drives cancer by subverting multiple tumor suppression pathways.

Front Oncol Lisek K, Campaner E, Ciani Y, Walerych D, Del Sal G Mutant p53 tunes the NRF2-dependent antioxidant response to support survival of cancer cells. Oncotarget Du X, Fu X, Yao K, Lan Z, Xu H, Cui Q, Yang E Bcl-2 delays cell cycle through mitochondrial ATP and ROS.

Cell Cycle — Liang J, Cao R, Wang X, Zhang Y, Wang P, Gao H, Li C, Yang F, Zeng R, Wei P Mitochondrial PKM2 regulates oxidative stress-induced apoptosis by stabilizing Bcl2. Cell Res — Martin TA, Ye L, Sanders AJ, Lane J, Jiang WG Cancer invasion and metastasis: molecular and cellular perspective.

In: Madame Curie bioscience database [Internet]. Landes Bioscience, Austin. Seyfried TN, Huysentruyt LC On the origin of cancer metastasis. Crit Rev Oncog Lambert AW, Pattabiraman DR, Weinberg RA Emerging biological principles of metastasis.

Cell — Baba AI, Câtoi C Tumor cell morphology. In: Comparative oncology. The Publishing House of the Romanian Academy, Bucharest. Heerboth S, Housman G, Leary M, Longacre M, Byler S, Lapinska K, Willbanks A, Sarkar S EMT and tumor metastasis.

Clin Transl Med Mittal V Epithelial mesenchymal transition in tumor metastasis. Annu Rev Pathol — Wang H, Unternaehrer JJ Epithelial-mesenchymal transition and cancer stem cells: at the crossroads of differentiation and dedifferentiation. Dev Dyn — Nagarsheth N, Wicha MS, Zou W Chemokines in the cancer microenvironment and their relevance in cancer immunotherapy.

Nat Rev Immunol Mol Med Rep — Liao Z, Chua D, Tan NS Reactive oxygen species: a volatile driver of field cancerization and metastasis. Miyazaki Y, Hara A, Kato K, Oyama T, Yamada Y, Mori H, Shibata T The effect of hypoxic microenvironment on matrix metalloproteinase expression in xenografts of human oral squamous cell carcinoma.

Int J Oncol — Zhang L, Huang G, Li X, Zhang Y, Jiang Y, Shen J, Liu J, Wang Q, Zhu J, Feng X Hypoxia induces epithelial-mesenchymal transition via activation of SNAI1 by hypoxia-inducible factor-1α in hepatocellular carcinoma.

BMC Cancer Nishida N, Kudo M Oxidative stress and epigenetic instability in human hepatocarcinogenesis. Dig Dis — Nishida N, Yano H, Nishida T, Kamura T, Kojiro MJ Angiogenesis in cancer. Vasc Health Risk Manag Kim Y-W, Byzova TVJB Oxidative stress in angiogenesis and vascular disease.

Blood — Carmeliet PJ VEGF as a key mediator of angiogenesis in cancer. Oncology — Babior BM NADPH oxidase. Curr Opin Immunol — Xia C, Meng Q, Liu LZ, Rojanasakul Y, Wang XR, Jiang BH Reactive oxygen species regulate angiogenesis and tumor growth through vascular endothelial growth factor.

Cancer Res — Sun X, Wei J, Tang Y, Wang B, Zhang Y, Shi L, Guo J, Hu F, Li X Leptin-induced migration and angiogenesis in rheumatoid arthritis is mediated by reactive oxygen species.

FEBS Open Bio — Coussens LM, Werb Z Inflammation and cancer. Nature Blaylock RL Cancer microenvironment, inflammation and cancer stem cells: a hypothesis for a paradigm change and new targets in cancer control. Surg Neurol Int Landskron G, De la Fuente M, Thuwajit P, Thuwajit C, Hermoso MA Chronic inflammation and cytokines in the tumor microenvironment.

J Immunol Res Hanahan D, Weinberg RA Hallmarks of cancer: the next generation. Kiraly O, Gong G, Olipitz W, Muthupalani S, Engelward BP Inflammation-induced cell proliferation potentiates DNA damage-induced mutations in vivo. PLoS Genet e Mantovani A, Allavena P, Sica A, Balkwill F Cancer-related inflammation.

Grivennikov SI, Greten FR, Karin M Immunity, inflammation, and cancer. Kim SS, Ruiz VE, Carroll JD, Moss SF Helicobacter pylori in the pathogenesis of gastric cancer and gastric lymphoma.

Wroblewski LE, Peek RM, Wilson KT Helicobacter pylori and gastric cancer: factors that modulate disease risk. Clin Microbiol Rev — Arbuthnot P, Kew M Hepatitis B virus and hepatocellular carcinoma.

Int J Exp Pathol — El-Serag HB Hepatocellular carcinoma and hepatitis C in the United States. Hepatology — de Martel C, Franceschi S Infections and cancer: established associations and new hypotheses.

Crit Rev Oncol Hematol — Balkwill F, Mantovani A Inflammation and cancer: back to Virchow? Lancet — Stark T, Livas L, Kyprianou N Inflammation in prostate cancer progression and therapeutic targeting. Transl Androl Urol Shrihari T Dual role of inflammatory mediators in cancer.

Ecancermedicalscience Hoesel B, Schmid JA The complexity of NF-κB signaling in inflammation and cancer. Mogensen TH Pathogen recognition and inflammatory signaling in innate immune defenses.

Franchi L, Eigenbrod T, Muñoz-Planillo R, Nuñez G The inflammasome: a caspaseactivation platform that regulates immune responses and disease pathogenesis.

Nat Immunol — Fialkow L, Wang Y, Downey GP Reactive oxygen and nitrogen species as signaling molecules regulating neutrophil function. Salzano S, Checconi P, Hanschmann E-M, Lillig CH, Bowler LD, Chan P, Vaudry D, Mengozzi M, Coppo L, Sacre S Linkage of inflammation and oxidative stress via release of glutathionylated peroxiredoxin-2, which acts as a danger signal.

Proc Natl Acad Sci — PubMed CAS PubMed Central Google Scholar. Martinon F Signaling by ROS drives inflammasome activation. Eur J Immunol — Latz E, Xiao TS, Stutz A Activation and regulation of the inflammasomes.

Nat Rev Immunol — Zhou R, Tardivel A, Thorens B, Choi I, Tschopp J Thioredoxin-interacting protein links oxidative stress to inflammasome activation.

Nat Immunol Zhou R, Yazdi AS, Menu P, Tschopp J A role for mitochondria in NLRP3 inflammasome activation. Nature — Ghezzi P Role of glutathione in immunity and inflammation in the lung. Int J Gen Med Morgan MJ, Liu Z-G Crosstalk of reactive oxygen species and NF-κB signaling.

Blanco P, Palucka AK, Pascual V, Banchereau J Dendritic cells and cytokines in human inflammatory and autoimmune diseases. Cytokine Growth Factor Rev — Klampfer L Cytokines, inflammation and colon cancer.

Curr Cancer Drug Targets — Liang M, Zhang P, Fu J Up-regulation of LOX-1 expression by TNF-α promotes trans-endothelial migration of MDA-MB breast cancer cells. Zamarron BF, Chen W Dual roles of immune cells and their factors in cancer development and progression.

Int J Biol Sci Lin W-W, Karin M A cytokine-mediated link between innate immunity, inflammation, and cancer. J Clin Investig Knüpfer H, Preiss R Serum interleukin-6 levels in colorectal cancer patients—a summary of published results.

Int J Colorectal Dis — Tanaka T, Bai Z, Srinoulprasert Y, Yang B, Hayasaka H, Miyasaka M Chemokines in tumor progression and metastasis. Cancer Sci — Yu JH, Kim H Oxidative stress and cytokines in the pathogenesis of pancreatic cancer. J Cancer Prev Prawan A, Buranrat B, Kukongviriyapan U, Sripa B, Kukongviriyapan V Inflammatory cytokines suppress NAD P H: quinone oxidoreductase-1 and induce oxidative stress in cholangiocarcinoma cells.

J Cancer Res Clin Oncol — Oncol Rep — Esquivel-Velázquez M, Ostoa-Saloma P, Palacios-Arreola MI, Nava-Castro KE, Castro JI, Morales-Montor J The role of cytokines in breast cancer development and progression. J Interferon Cytokine Res — Wojdasiewicz P, Poniatowski ŁA, Szukiewicz D The role of inflammatory and anti-inflammatory cytokines in the pathogenesis of osteoarthritis.

Mediators Inflamm Ravichandran K, Tyagi A, Deep G, Agarwal C, Agarwal R Interleukininduced iNOS expression in human lung carcinoma A cells: involvement of STAT and MAPK pathways. Scheller J, Chalaris A, Schmidt-Arras D, Rose-John S The pro-and anti-inflammatory properties of the cytokine interleukin Biochim Biophys Acta Mol Cell Res — Brizzi MF, Formato L, Dentelli P, Rosso A, Pavan M, Garbarino G, Pegoraro M, Camussi G, Pegoraro L Interleukin-3 stimulates migration and proliferation of vascular smooth muscle cells.

Circulation — Ehrlich LA, Chung HY, Ghobrial I, Choi SJ, Morandi F, Colla S, Rizzoli V, Roodman GD, Giuliani N IL-3 is a potential inhibitor of osteoblast differentiation in multiple myeloma. Gupta N, Barhanpurkar AP, Tomar GB, Srivastava RK, Kour S, Pote ST, Mishra GC, Wani MR IL-3 inhibits human osteoclastogenesis and bone resorption through downregulation of c-Fms and diverts the cells to dendritic cell lineage.

J Immunol — Heikkilä K, Ebrahim S, Lawlor DA Systematic review of the association between circulating interleukin-6 IL-6 and cancer. Eur J Cancer — Hodge DR, Hurt EM, Farrar WL The role of IL-6 and STAT3 in inflammation and canicer. Aggarwal BB, Sethi G, Ahn KS, Sandur SK, Pandey MK, Kunnumakkara AB, Sung B, Ichikawa H Targeting signal-transducer-and-activator-of-transcription-3 for prevention and therapy of cancer.

Rao V, Dyer C, Jameel J, Drew P, Greenman J Potential prognostic and therapeutic roles for cytokines in breast cancer. J Clin Oncol — Kinoshita H, Hirata Y, Nakagawa H, Sakamoto K, Hayakawa Y, Takahashi R, Nakata W, Sakitani K, Serizawa T, Hikiba Y Interleukin-6 mediates epithelial—stromal interactions and promotes gastric tumorigenesis.

PLoS One 8:e Gasche JA, Hoffmann J, Boland CR, Goel A Interleukin-6 promotes tumorigenesis by altering DNA methylation in oral cancer cells.

Int J Cancer — Baffet G, Braciak T, Fletcher R, Gauldie J, Fey G, Northemann W Autocrine activity of interleukin 6 secreted by hepatocarcinoma cell lines. Mol Biol Med — Atreya R, Mudter J, Finotto S, Müllberg J, Jostock T, Wirtz S, Schütz M, Bartsch B, Holtmann M, Becker C Blockade of interleukin 6 trans signaling suppresses T-cell resistance against apoptosis in chronic intestinal inflammation: evidence in crohn disease and experimental colitis in vivo.

Nat Med Becker C, Fantini MC, Schramm C, Lehr HA, Wirtz S, Nikolaev A, Burg J, Strand S, Kiesslich R, Huber S TGF-β suppresses tumor progression in colon cancer by inhibition of IL-6 trans-signaling. Immunity — McGeachy MJ, Bak-Jensen KS, Chen Y, Tato CM, Blumenschein W, McClanahan T, Cua DJ TGF-[beta] and IL-6 drive the production of IL and IL by T cells and restrain TH cell-mediated pathology.

Onishi RM, Gaffen SL Interleukin and its target genes: mechanisms of interleukin function in disease. Immunology — Drug Des Devel Ther Maniati E, Soper R, Hagemann T Up for Mischief?

Oncogene Infect Agent Cancer Numasaki M, Fukushi J-I, Ono M, Narula SK, Zavodny PJ, Kudo T, Robbins PD, Tahara H, Lotze MT Interleukin promotes angiogenesis and tumor growth.

Kolls JK, Lindén A Interleukin family members and inflammation. Kryczek I, Wei S, Zou L, Altuwaijri S, Szeliga W, Kolls J, Chang A, Zou W Cutting edge: Th17 and regulatory T cell dynamics and the regulation by IL-2 in the tumor microenvironment. Swann JB, Smyth MJ Immune surveillance of tumors.

Meier B, Radeke H, Selle S, Younes M, Sies H, Resch K, Habermehl G Human fibroblasts release reactive oxygen species in response to interleukin-1 or tumour necrosis factor-α. Biochem J — Li Q, Engelhardt JF Interleukin-1β induction of NFκB is partially regulated by H2O2-mediated activation of NFκB-inducing kinase.

J Biol Chem — Hsu S, Hsu P Autocrine and paracrine functions of cytokines in malignant lymphomas. Biomed Pharmacother — Endocrinology — Yuzhalin A, Kutikhin A Interleukins in cancer biology: their heterogeneous role.

Academic, Cambridge. Szlosarek P, Charles KA, Balkwill FR Tumour necrosis factor-α as a tumour promoter. Szlosarek PW, Balkwill FR Tumour necrosis factor α: a potential target for the therapy of solid tumours. Lancet Oncol — Leek R, Landers R, Fox S, Ng F, Harris A, Lewis C Association of tumour necrosis factor alpha and its receptors with thymidine phosphorylase expression in invasive breast carcinoma.

Br J Cancer Sethi G, Sung B, Aggarwal BB TNF: a master switch for inflammation to cancer. Dempsey PW, Doyle SE, He JQ, Cheng G The signaling adaptors and pathways activated by TNF superfamily. Aggarwal BB Signalling pathways of the TNF superfamily: a double-edged sword.

Aggarwal BB, Shishodia S, Ashikawa K, Bharti AC The role of TNF and its family members in inflammation and cancer: lessons from gene deletion. Curr Drug Targets Inflamm Allergy — Wajant H, Pfizenmaier K, Scheurich P Tumor necrosis factor signaling.

Cell Death Differ Wang X, Lin Y Tumor necrosis factor and cancer, buddies or foes? Acta Pharmacol Sin — Devin A, Cook A, Lin Y, Rodriguez Y, Kelliher M, Liu Z-G The distinct roles of TRAF2 and RIP in IKK activation by TNF-R1: TRAF2 recruits IKK to TNF-R1 while RIP mediates IKK activation.

Yang J, Lin Y, Guo Z, Cheng J, Huang J, Deng L, Liao W, Chen Z, Zheng-gang L, Su B The essential role of MEKK3 in TNF-induced NF-[kappa] B activation. Karin M, Yamamoto Y, Wang QM The IKK NF-[kappa] B system: a treasure trove for drug development.

Nat Rev Drug Discov Kamata H, Honda S-I, Maeda S, Chang L, Hirata H, Karin M Reactive oxygen species promote TNFα-induced death and sustained JNK activation by inhibiting MAP kinase phosphatases. Reinhard C, Shamoon B, Shyamala V, Williams LT Tumor necrosis factor α-induced activation of c-jun N-terminal kinase is mediated by TRAF2.

EMBO J — Liu J, Lin A Role of JNK activation in apoptosis: a double-edged sword. Cell Res Shih R-H, Wang C-Y, Yang C-M NF-kappaB signaling pathways in neurological inflammation: a mini review. Front Mol Neurosci Alkhamesi NA, Ziprin P, Pfistermuller K, Peck DH, Darzi AW ICAM-1 mediated peritoneal carcinomatosis, a target for therapeutic intervention.

Clin Exp Metastasis — Choo MK, Sakurai H, Koizumi K, Saiki I TAK1-mediated stress signaling pathways are essential for TNF-α-promoted pulmonary metastasis of murine colon cancer cells. Kitakata H, Nemoto-Sasaki Y, Takahashi Y, Kondo T, Mai M, Mukaida N Essential roles of tumor necrosis factor receptor p55 in liver metastasis of intrasplenic administration of colon 26 cells.

Kulbe H, Hagemann T, Szlosarek PW, Balkwill FR, Wilson JL The inflammatory cytokine tumor necrosis factor-α regulates chemokine receptor expression on ovarian cancer cells. Mochizuki Y, Nakanishi H, Kodera Y, Ito S, Yamamura Y, Kato T, Hibi K, Akiyama S, Nakao A, Tatematsu M TNF-α promotes progression of peritoneal metastasis as demonstrated using a green fluorescence protein GFP -tagged human gastric cancer cell line.

Van Grevenstein W, Hofland L, Van Rossen M, Van Koetsveld P, Jeekel J, Van Eijck C Inflammatory cytokines stimulate the adhesion of colon carcinoma cells to mesothelial monolayers.

Dig Dis Sci — Ziprin P, Ridgway PF, Pfistermüller KL, Peck DH, Darzi AW ICAM-1 mediated tumor-mesothelial cell adhesion is modulated by IL-6 and TNF-α: a potential mechanism by which surgical trauma increases peritoneal metastases.

Cell Commun Adhes — Balkwill F Tumour necrosis factor and cancer. Nat Rev Cancer Kehrl JH, Wakefield LM, Roberts AB, Jakowlew S, Alvarez-Mon M, Derynck R, Sporn MB, Fauci AS Production of transforming growth factor beta by human T lymphocytes and its potential role in the regulation of T cell growth.

J Exp Med — Roberts AB, Sporn MB, Assoian RK, Smith JM, Roche NS, Wakefield LM, Heine UI, Liotta LA, Falanga V, Kehrl JH Transforming growth factor type beta: rapid induction of fibrosis and angiogenesis in vivo and stimulation of collagen formation in vitro.

Letterio JJ TGF-[beta] signaling in T cells: roles in lymphoid and epithelial neoplasia. Bierie B, Moses HL TGF-β and cancer.

Levy L, Hill CS Alterations in components of the TGF-β superfamily signaling pathways in human cancer. Valle L, Serena-Acedo T, Liyanarachchi S, Hampel H, Comeras I, Li Z, Zeng Q, Zhang H-T, Pennison MJ, Sadim M Germline allele-specific expression of TGFBR1 confers an increased risk of colorectal cancer.

Zeng Q, Phukan S, Xu Y, Sadim M, Rosman DS, Pennison M, Liao J, Yang G-Y, Huang C-C, Valle L Tgfbr1 haploinsufficiency is a potent modifier of colorectal cancer development. Bierie B, Moses HL Tumour microenvironment: TGF [beta]: the molecular Jekyll and Hyde of cancer.

Brandes M, Mai U, Ohura K, Wahl S Type I transforming growth factor-beta receptors on neutrophils mediate chemotaxis to transforming growth factor-beta. Wahl SM, Hunt DA, Wakefield LM, McCartney-Francis N, Wahl LM, Roberts AB, Sporn MB Transforming growth factor type beta induces monocyte chemotaxis and growth factor production.

Gruber BL, Marchese MJ, Kew RR Transforming growth factor-beta 1 mediates mast cell chemotaxis. Li MO, Wan YY, Sanjabi S, Robertson A-KL, Flavell RA Transforming growth factor-β regulation of immune responses.

Annu Rev Immunol — Maghazachi A, Al-Aoukaty A Transforming growth factor-beta 1 is chemotactic for interleukinactivated natural killer cells. Nat Immun — Wrzesinski SH, Wan YY, Flavell RA Transforming growth factor-β and the immune response: implications for anticancer therapy.

Clin Cancer Res — Bierie B, Moses HL Transforming growth factor beta TGF-β and inflammation in cancer. Liu R-M, Pravia KG Oxidative stress and glutathione in TGF-β-mediated fibrogenesis. Tochhawng L, Deng S, Pervaiz S, Yap CT Redox regulation of cancer cell migration and invasion. Mitochondrion — Krstić J, Trivanović D, Mojsilović S, Santibanez JF Transforming growth factor-beta and oxidative stress interplay: implications in tumorigenesis and cancer progression.

Zlotnik A Chemokines and cancer. Stone MJ, Hayward JA, Huang C, Huma ZE, Sanchez J Mechanisms of regulation of the chemokine-receptor network.

Int J Mol Sci PubMed Central Google Scholar. Dubinett SM, Lee J, Sharma S, Mulé JJ Chemokines: can effector cells be re-directed to the site of tumor? Cancer J Martins-Green M, Petreaca M, Wang L Chemokines and their receptors are key players in the orchestra that regulates wound healing.

Adv Wound Care — Proost P, Wuyts A, Van Damme J The role of chemokines in inflammation. Int J Clin Lab Res — Rossi D, Zlotnik A The biology of chemokines and their receptors. Chetram MA, Hinton CV ROS-mediated regulation of CXCR4 in cancer.

Front Biol — Salazar N, Castellan M, Shirodkar SS, Lokeshwar BL Chemokines and chemokine receptors as promoters of prostate cancer growth and progression.

Crit Rev Eukaryot Gene Expr — Strieter RM, Gomperts BN, Keane MP The role of CXC chemokines in pulmonary fibrosis. Clarke CN, Kuboki S, Tevar A, Lentsch AB, Edwards M Roles of NF-kappaB and STAT3 in CXC chemokine—mediated hepatocyte proliferation and cell death.

J Am Coll Surg S Article Google Scholar. Richmond A NF-κB, chemokine gene transcription and tumour growth. Murphy PM, Baggiolini M, Charo IF, Hébert CA, Horuk R, Matsushima K, Miller LH, Oppenheim JJ, Power CA International union of pharmacology. XXII Nomenclature for chemokine receptors.

Pharmacol Rev — Zlotnik A, Yoshie O Chemokines: a new classification system and their role in immunity. Balkwill F Cancer and the chemokine network. Bottazzi B, Polentarutti N, Acero R, Balsari A, Boraschi D, Ghezzi P, Salmona M, Mantovani A Regulation of the macrophage content of neoplasms by chemoattractants.

Pollard JW Tumour-educated macrophages promote tumour progression and metastasis. Germano G, Frapolli R, Simone M, Tavecchio M, Erba E, Pesce S, Pasqualini F, Grosso F, Sanfilippo R, Casali PG Antitumor and anti-inflammatory effects of trabectedin on human myxoid liposarcoma cells.

Soucek L, Lawlor ER, Soto D, Shchors K, Swigart LB, Evan GI Mast cells are required for angiogenesis and macroscopic expansion of Myc-induced pancreatic islet tumors. Ghadjar P, Coupland SE, Na I-K, Noutsias M, Letsch A, Stroux A, Bauer S, Buhr HJ, Thiel E, Scheibenbogen C Chemokine receptor CCR6 expression level and liver metastases in colorectal cancer.

Marchesi F, Piemonti L, Fedele G, Destro A, Roncalli M, Albarello L, Doglioni C, Anselmo A, Doni A, Bianchi P The chemokine receptor CX3CR1 is involved in the neural tropism and malignant behavior of pancreatic ductal adenocarcinoma.

Singh S, Nannuru K, Sadanandam A, Varney M, Singh R CXCR1 and CXCR2 enhances human melanoma tumourigenesis, growth and invasion. Wang J, Seethala RR, Zhang Q, Gooding W, Van Waes C, Hasegawa H, Ferris RL Autocrine and paracrine chemokine receptor 7 activation in head and neck cancer: implications for therapy.

J Natl Cancer Inst — Murakami T, Cardones AR, Finkelstein SE, Restifo NP, Klaunberg BA, Nestle FO, Castillo SS, Dennis PA, Hwang ST Immune evasion by murine melanoma mediated through CC chemokine receptor Kwong J, Kulbe H, Wong D, Chakravarty P, Balkwill F An antagonist of the chemokine receptor CXCR4 induces mitotic catastrophe in ovarian cancer cells.

Mol Cancer Ther — Kalluri R, Zeisberg M Fibroblasts in cancer. CAS PubMed Google Scholar. Gialeli C, Theocharis AD, Karamanos NK Roles of matrix metalloproteinases in cancer progression and their pharmacological targeting.

Van Lint P, Libert C Chemokine and cytokine processing by matrix metalloproteinases and its effect on leukocyte migration and inflammation. J Leukoc Biol — Deryugina EI, Quigley JP Tumor angiogenesis: MMP-mediated induction of intravasation-and metastasis-sustaining neovasculature.

Matrix Biol — PLoS One 4:e de Souza Junior DA, Santana AC, da Silva EZM, Oliver C, Jamur MC The role of mast cell specific chymases and tryptases in tumor angiogenesis. Biomed Res Int. Mori K, Shibanuma M, Nose K Invasive potential induced under long-term oxidative stress in mammary epithelial cells.

Westermarck J, KÄHÄRI V-M Regulation of matrix metalloproteinase expression in tumor invasion. FASEB J — Swanson KV, Deng M, Ting JP-Y The NLRP3 inflammasome: molecular activation and regulation to therapeutics.

Lin C, Zhang J Inflammasomes in inflammation-induced cancer. Front Immunol Abais JM, Xia M, Zhang Y, Boini KM, Li P-L Redox regulation of NLRP3 inflammasomes: ROS as trigger or effector? Dostert C, Pétrilli V, Van Bruggen R, Steele C, Mossman BT, Tschopp J Innate immune activation through Nalp3 inflammasome sensing of asbestos and silica.

Szabo G, Petrasek J Inflammasome activation and function in liver disease. Nat Rev Gastroenterol Hepatol Zhong Z, Zhai Y, Liang S, Mori Y, Han R, Sutterwala FS, Qiao L TRPM2 links oxidative stress to NLRP3 inflammasome activation.

Nat Commun — Download references. Cell Biology Laboratory, School of Biological Sciences and Biotechnology, Indian Institute of Advanced Research, Gandhinagar, Gujarat, India. Foram U. Clinical Genomics Center Mount Sinai Hospital, Toronto, ON, Canada. You can also search for this author in PubMed Google Scholar.

Correspondence to Chandramani Pathak. Department of Biochemistry, Central University of Haryana, Mahendergarh, Haryana, India. Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Sydney, NSW, Australia. Reprints and permissions. Vaidya, F.

Oxidative Stress and Inflammation Can Fuel Cancer. In: Maurya, P. eds Role of Oxidative Stress in Pathophysiology of Diseases. Springer, Singapore. Published : 16 June

Eur J Med Chem. Bieging KT, Mello SS, Attardi LD. Unravelling mechanisms of pmediated tumour suppression. Nat Rev Cancer. Liang Y, Liu J, Feng Z. The regulation of cellular metabolism by tumor suppressor p Cell Biosci.

Srinivas US, Tan BW, Vellayappan BA, Jeyasekharan AD. ROS and the DNA damage response in cancer. Redox Biol. Maxwell KN, Cheng HH, Powers J, Gulati R, Ledet EM, Morrison C, LE A, Hausler R, Stopfer J, Hyman S. Inherited TP53 variants and risk of prostate Cancer.

Eur Urol. Morris LG, Chan TA. Therapeutic targeting of tumor suppressor genes. Puzio-Kuter AM, Castillo-Martin M, Kinkade CW, Wang X, Shen TH, Matos T, Shen MM, Cordon-Cardo C, Abate-Shen C. Inactivation of p53 and Pten promotes invasive bladder cancer.

Genes Dev. Wang B. BRCA1 tumor suppressor network: focusing on its tail. Bae I, Fan S, Meng Q, Rih JK, Kim HJ, Kang HJ, Xu J, Goldberg ID, Jaiswal AK, Rosen EM. BRCA1 induces antioxidant gene expression and resistance to oxidative stress.

Cancer Res. Sundararajan S, Ahmed A, Goodman OB Jr. The relevance of BRCA genetics to prostate cancer pathogenesis and treatment. Clin Adv Hematol Oncol. PubMed Google Scholar. Yi YW, Kang HJ, Bae I. BRCA1 and oxidative stress. Fridlich R, Annamalai D, Roy R, Bernheim G, Powell SN.

BRCA1 and BRCA2 protect against oxidative DNA damage converted into double-strand breaks during DNA replication. DNA Repair. Mersch J, Jackson MA, Park M, Nebgen D, Peterson SK, Singletary C, Arun BK, Litton JK. Cancers associated with BRCA 1 and BRCA 2 mutations other than breast and ovarian.

Menegon S, Columbano A, Giordano S. The dual roles of NRF2 in cancer. Trends Mol Med. de La Vega MR, Chapman E, Zhang DD. NRF2 and the hallmarks of cancer. Article PubMed Central Google Scholar. Choi B-H, Kwak M-K. Shadows of NRF2 in cancer: resistance to chemotherapy. Jung B-J, Yoo H-S, Shin S, Park Y-J, Jeon S-M.

Dysregulation of NRF2 in cancer: from molecular mechanisms to therapeutic opportunities. Biomol Ther. Article CAS Google Scholar. Indovina P, Pentimalli F, Casini N, Vocca I, Giordano A. RB1 dual role in proliferation and apoptosis: cell fate control and implications for cancer therapy.

Macleod KF. The role of the RB tumour suppressor pathway in oxidative stress responses in the haematopoietic system. di Fiore R, D'Anneo A, Tesoriere G, Vento R.

RB1 in cancer: different mechanisms of RB1 inactivation and alterations of pRb pathway in tumorigenesis. J Cell Physiol. Article PubMed Google Scholar. Villeneuve NF, Sun Z, Chen W, Zhang DD. Nrf2 and p21 regulate the fine balance between life and death by controlling ROS levels.

Book Google Scholar. He S, Liu M, Zhang W, Xu N, Zhu H. Over expression of pactivated kinase 7 associates with lymph node metastasis in esophageal squamous cell cancers.

Cancer Biomarkers. Jing Z, You-Hong J, Wei Z. Expression of p21 and p15 in gastric cancer patients. Aceto GM, Catalano T, Curia MC. Molecular aspects of colorectal adenomas: the interplay among microenvironment, oxidative stress, and predisposition.

BioMed Res Int. Qin R-F, Zhang J, Huo H-R, Yuan Z-J, Xue J-D. MiR mediated APC regulation contributes to pancreatic cancer cell proliferation. World J Gastroenterol. Donkena KV, Young CY, Tindall DJ. Oxidative stress and DNA methylation in prostate cancer. Obstet Gynecol Int. Fang Z, Xiong Y, Li J, Liu L, Zhang W, Zhang C, Wan J.

APC gene deletions in gastric adenocarcinomas in a Chinese population: a correlation with tumour progression. Clin Transl Oncol. Davee T, Coronel E, Papafragkakis C, Thaiudom S, Lanke G, Chakinala RC, González GMN, Bhutani MS, Ross WA, Weston BR.

Pancreatic cancer screening in high-risk individuals with germline genetic mutations. Gastrointest Endosc. Aghabozorgi AS, Bahreyni A, Soleimani A, Bahrami A, Khazaei M, Ferns GA, Avan A, Hassanian SM. Role of adenomatous polyposis coli APC gene mutations in the pathogenesis of colorectal cancer; current status and perspectives.

Hankey W, Frankel WL, Groden J. Functions of the APC tumor suppressor protein dependent and independent of canonical WNT signaling: implications for therapeutic targeting.

Cancer Metastasis Rev. Narayan S, Sharma R. Molecular mechanism of adenomatous polyposis coli-induced blockade of base excision repair pathway in colorectal carcinogenesis. Life Sci. Katerji M, Filippova M, Duerksen-Hughes P.

Approaches and methods to measure oxidative stress in clinical samples: research applications in the Cancer field. Chiorcea-Paquim A-M. Milkovic L, Zarkovic N, Marusic Z, Zarkovic K, Jaganjac M. The 4-Hydroxynonenal-protein adducts and their biological relevance: are some proteins preferred targets?

Liu Y, Al-Adra DP, Lan R, Jung G, Li H, Yeh MM, Liu YZ. RNA sequencing analysis of hepatocellular carcinoma identified oxidative phosphorylation as a major pathologic feature. Hepatol Commun. Jiang C, Qian M, Gocho Y, Yang W, Du G, Shen S, Yang JJ, Zhang H.

Blood Adv. Pimkova K, Jassinskaja M, Munita R, Ciesla M, Guzzi N, Cao Thi Ngoc P, Vajrychova M, Johansson E, Bellodi C, Hansson J. Quantitative analysis of redox proteome reveals oxidation-sensitive protein thiols acting in fundamental processes of developmental hematopoiesis. Higgins L, Gerdes H, Cutillas PR.

Principles of phosphoproteomics and applications in cancer research. Biochem J. Serafimov K, Aydin Y, Lämmerhofer M. Quantitative analysis of the glutathione pathway cellular metabolites by targeted liquid chromatography - tandem mass spectrometry.

J Sep Sci. Wang Z, Ma P, Wang Y, Hou B, Zhou C, Tian H, Li B, Shui G, Yang X, Qiang G, Yin C, Du G. Untargeted metabolomics and transcriptomics identified glutathione metabolism disturbance and PCS and TMAO as potential biomarkers for ER stress in lung.

Sci Rep. Greenwood HE, Witney TH. Latest advances in imaging oxidative stress in Cancer. J Nucl Med. Ghasemitarei M, Ghorbi T, Yusupov M, Zhang Y, Zhao T, Shali P, Bogaerts A. Effects of nitro-oxidative stress on biomolecules: part 1-non-reactive molecular dynamics simulations. Wang W, Rong Z, Wang G, Hou Y, Yang F, Qiu M.

Cancer metabolites: promising biomarkers for cancer liquid biopsy. Biomarker Res. Perillo B, di Donato M, Pezone A, di Zazzo E, Giovannelli P, Galasso G, Castoria G, Migliaccio A. ROS in cancer therapy: the bright side of the moon.

Exp Mol Med. Raza MH, Siraj S, Arshad A, Waheed U, Aldakheel F, Alduraywish S, Arshad M. ROS-modulated therapeutic approaches in cancer treatment. J Cancer Res Clin Oncol. Somu P, Mohanty S, Paul S. A detailed overview of ROS-modulating approaches in Cancer treatment: Nano-based system to improve its future clinical perspective.

Handbook of Oxidative Stress in Cancer: Therapeutic Aspects; Sofiullah SSM, Murugan DD, Muid SA, Seng WY, Kadir SZSA, Abas R, Ridzuan NRA, Zamakshshari NH, Woon CK. Natural bioactive compounds targeting NADPH oxidase pathway in cardiovascular diseases. Forman HJ, Zhang H. Targeting oxidative stress in disease: promise and limitations of antioxidant therapy.

Nat Rev Drug Discov. Nizami ZN, Aburawi HE, Semlali A, Muhammad K, Iratni R. Oxidative stress inducers in Cancer therapy: preclinical and clinical evidence.

Li Y, Zhang X, Wang Z, Li B, Zhu H. Modulation of redox homeostasis: A strategy to overcome cancer drug resistance. Anwanwan D, Singh SK, Singh S, Saikam V, Singh R. Challenges in liver cancer and possible treatment approaches.

Biochim Biophys Acta BBA -Rev Cancer. Chehelgerdi M, Chehelgerdi M, Allela OQB, Pecho RDC, Jayasankar N, Rao DP, Thamaraikani T, Vasanthan M, Viktor P, Lakshmaiya N, Saadh MJ, Amajd A, Abo-Zaid MA, Castillo-Acobo RY, Ismail AH, Amin AH, Akhavan-Sigari R.

Progressing nanotechnology to improve targeted cancer treatment: overcoming hurdles in its clinical implementation. Mol Cancer. Wu C, Mao J, Wang X, Yang R, Wang C, Li C, Zhou X. Advances in treatment strategies based on scavenging reactive oxygen species of nanoparticles for atherosclerosis.

J Nanobiotechnol. Iqbal MJ, Ali S, Rashid U, Kamran M, Malik MF, Sughra K, Zeeshan N, Afroz A, Saleem J, Saghir M. Biosynthesis of silver nanoparticles from leaf extract of Litchi chinensis and its dynamic biological impact on microbial cells and human cancer cell lines.

Cell Mol Biol. Rejinold NS, Muthunarayanan M, Divyarani V, Sreerekha P, Chennazhi K, Nair S, Tamura H, Jayakumar R. Curcumin-loaded biocompatible thermoresponsive polymeric nanoparticles for cancer drug delivery.

J Colloid Interface Sci. Javid H, Hashemy SI, Heidari MF, Esparham A, Gorgani-Firuzjaee S. The anticancer role of cerium oxide nanoparticles by inducing antioxidant activity in esophageal Cancer and Cancer stem-like ESCC spheres. Biomed Res Int. Bonet-Aleta J, Calzada-Funes J, Hueso JL.

Manganese oxide nano-platforms in cancer therapy: recent advances on the development of synergistic strategies targeting the tumor microenvironment. Appl Mater Today.

Chasara RS, Ajayi TO, Leshilo DM, Poka MS, Witika BA. Exploring novel strategies to improve anti-tumour efficiency: the potential for targeting reactive oxygen species. Čapek J, Roušar T. Detection of oxidative stress induced by nanomaterials in cells—the roles of reactive oxygen species and glutathione.

Bigham A, Raucci MG. Multi-responsive materials: properties, design, and applications. In: Stimuli-Responsive Materials for Biomedical Applications.

American Chemical Society; Teixeira PV, Fernandes E, Soares TB, Adega F, Lopes CM, Lúcio M. Natural compounds: co-delivery strategies with chemotherapeutic agents or nucleic acids using lipid-based Nanocarriers. Craddock CF, Houlton AE, Quek LS, Ferguson P, Gbandi E, Roberts C, Metzner M, Garcia-Martin N, Kennedy A, Hamblin A, Raghavan M, Nagra S, Dudley L, Wheatley K, Mcmullin MF, Pillai SP, Kelly RJ, Siddique S, Dennis M, Cavenagh JD, Vyas P.

Outcome of Azacitidine therapy in acute myeloid leukemia is not improved by concurrent Vorinostat therapy but is predicted by a diagnostic molecular signature. Clin Cancer Res. Patnaik E, Madu C, Lu Y. Epigenetic modulators as therapeutic agents in Cancer.

Int J Mol Sci. Rullo R, Cerchia C, Nasso R, Romanelli V, Vendittis E, Masullo M, Lavecchia A. Novel reversible inhibitors of xanthine oxidase targeting the active site of the enzyme. Liu J, Chen Z, Li Y, Zhao W, Wu J, Zhang Z. Singh K, Bhori M, Kasu YA, Bhat G, Marar T. Antioxidants as precision weapons in war against cancer chemotherapy induced toxicity - exploring the armoury of obscurity.

Saudi Pharm J. Tenório M, Graciliano NG, Moura FA, Oliveira ACM, Goulart MOF. N-acetylcysteine NAC : impacts on human health. Download references. Department of Biotechnology, University of Sialkot, Sialkot, Punjab, Pakistan.

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Iqbal, M. et al. Interplay of oxidative stress, cellular communication and signaling pathways in cancer. Cell Commun Signal 22 , 7 Download citation. Received : 05 July Accepted : 14 November Published : 02 January Anyone you share the following link with will be able to read this content:.

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Abstract Cancer remains a significant global public health concern, with increasing incidence and mortality rates worldwide. Video Abstract. Introduction Carcinogenesis is a complex multistage process that incorporates genetic mutations and abnormal cell division [ 1 ].

Full size image. Signaling pathways in oxidative stress and cancer MAPK pathway Mitogen-activated protein kinases MAPKs are key signaling molecules in the cellular response to oxidative stress.

Keap1-Nrf2 pathway Keap1-Nrf2 pathway is the main stress response pathway that is reported to be activated in cells in response to oxidative stress.

Tumor suppressor genes and oxidative stress: a mutual interplay in carcinogenesis Cells employ a sophisticated array of mechanisms to counterbalance reactive oxygen species ROS , oscillating between antioxidative strategies and the activation of tumor suppressor genes.

Table 1 Interplay of tumor suppressor genes and oxidative stress: key regulators, functions, and associated cancers Full size table. Methods for oxidative stress profiling in oncology Various approaches are reported to be utilized to evaluate the status of oxidative stress in clinical samples.

Table 2 Comprehensive methods for oxidative stress profiling in oncology Full size table. Treatment approaches to target oxidative stress and cancer Various treatment approaches have been incorporated to beat the cancer progression either in the form of chemotherapy, radiotherapy, hormonal therapy and combined therapies, to target various interlinked cancer signaling pathways.

Trends Biochem Sci — Dhup S, Dadhich RK, Porporato PE, Sonveaux P Multiple biological activities of lactic acid in cancer: influences on tumor growth, angiogenesis and metastasis. Curr Pharm Des — Ann Transl Med — Pathak C, Vinayak M Modulation of lactate dehydrogenase isozymes by modified base queuine.

Mol Biol Rep — Mohammad GH, Damink SO, Malago M, Dhar DK, Pereira SP Pyruvate kinase M2 and lactate dehydrogenase A are overexpressed in pancreatic cancer and correlate with poor outcome.

PLoS One e Hsu M-C, Hung W-C Pyruvate kinase M2 fuels multiple aspects of cancer cells: from cellular metabolism, transcriptional regulation to extracellular signaling. Mol Cancer Gui DY, Lewis CA, Vander Heiden MG Allosteric regulation of PKM2 allows cellular adaptation to different physiological states.

Sci Signal 6:pe7. Anastasiou D, Yu Y, Israelsen WJ, Jiang J-K, Boxer MB, Hong BS, Tempel W, Dimov S, Shen M, Jha A Pyruvate kinase M2 activators promote tetramer formation and suppress tumorigenesis.

Nat Chem Biol Anastasiou D, Poulogiannis G, Asara JM, Boxer MB, Jiang J-K, Shen M, Bellinger G, Sasaki AT, Locasale JW, Auld DSJS Inhibition of pyruvate kinase M2 by reactive oxygen species contributes to cellular antioxidant responses. Science — Finley LW, Carracedo A, Lee J, Souza A, Egia A, Zhang J, Teruya-Feldstein J, Moreira PI, Cardoso SM, Clish CB SIRT3 opposes reprogramming of cancer cell metabolism through HIF1α destabilization.

Fiaschi T, Chiarugi P Oxidative stress, tumor microenvironment, and metabolic reprogramming: a diabolic liaison. Int J Cell Biol Burdon RH, Gill V, Rice-Evans C Oxidative stress and tumour cell proliferation. Free Radic Res Commun — Kumari S, Badana AK, Malla R Reactive oxygen species: a key constituent in cancer survival.

Biomark Insights Storz P Reactive oxygen species in tumor progression. Front Biosci — Yang Y, Fang E, Luo J, Wu H, Jiang Y, Liu Y, Tong S, Wang Z, Zhou R, Tong Q The antioxidant alpha-lipoic acid inhibits proliferation and invasion of human gastric cancer cells via suppression of STAT3-mediated MUC4 gene expression.

Hamanaka RB, Chandel NS Mitochondrial reactive oxygen species regulate cellular signaling and dictate biological outcomes. Wang M, Kirk JS, Venkataraman S, Domann FE, Zhang HJ, Schafer FQ, Flanagan SW, Weydert CJ, Spitz DR, Buettner GR Manganese superoxide dismutase suppresses hypoxic induction of hypoxia-inducible factor-1 α and vascular endothelial growth factor.

Oncogene — Patterson JC, Joughin BA, van de Kooij B, Lim DC, Lauffenburger DA, Yaffe MB ROS and oxidative stress are elevated in mitosis during asynchronous cell cycle progression and are exacerbated by mitotic arrest. Cell Syst — Ranjan P, Anathy V, Burch PM, Weirather K, Lambeth JD, Heintz NH Redox-dependent expression of cyclin D1 and cell proliferation by Nox1 in mouse lung epithelial cells.

Exp Cell Res — Verbon EH, Post JA, Boonstra J The influence of reactive oxygen species on cell cycle progression in mammalian cells. Gene —6. Kelkel M, Schumacher M, Dicato M, Diederich M Antioxidant and anti-proliferative properties of lycopene.

Laphanuwat P, Likasitwatanakul P, Sittithumcharee G, Thaphaengphan A, Chomanee N, Suppramote O, Ketaroonrut N, Charngkaew K, Lam EW-F, Okada S Cyclin D1 depletion interferes with oxidative balance and promotes cancer cell senescence. J Cell Sci — Nutr J Kozlov SV, Waardenberg AJ, Engholm-Keller K, Arthur JW, Graham ME, Lavin M Reactive oxygen species ROS -activated ATM-dependent phosphorylation of cytoplasmic substrates identified by large-scale phosphoproteomics screen.

Mol Cell Proteomics — Mantovani F, Collavin L, Del Sal G Mutant p53 as a guardian of the cancer cell. Cell Death Differ — Ma Q Role of nrf2 in oxidative stress and toxicity. Annu Rev Pharmacol Toxicol — Haupt S, Raghu D, Haupt Y Mutant p53 drives cancer by subverting multiple tumor suppression pathways.

Front Oncol Lisek K, Campaner E, Ciani Y, Walerych D, Del Sal G Mutant p53 tunes the NRF2-dependent antioxidant response to support survival of cancer cells.

Oncotarget Du X, Fu X, Yao K, Lan Z, Xu H, Cui Q, Yang E Bcl-2 delays cell cycle through mitochondrial ATP and ROS. Cell Cycle — Liang J, Cao R, Wang X, Zhang Y, Wang P, Gao H, Li C, Yang F, Zeng R, Wei P Mitochondrial PKM2 regulates oxidative stress-induced apoptosis by stabilizing Bcl2.

Cell Res — Martin TA, Ye L, Sanders AJ, Lane J, Jiang WG Cancer invasion and metastasis: molecular and cellular perspective. In: Madame Curie bioscience database [Internet]. Landes Bioscience, Austin. Seyfried TN, Huysentruyt LC On the origin of cancer metastasis.

Crit Rev Oncog Lambert AW, Pattabiraman DR, Weinberg RA Emerging biological principles of metastasis. Cell — Baba AI, Câtoi C Tumor cell morphology. In: Comparative oncology. The Publishing House of the Romanian Academy, Bucharest. Heerboth S, Housman G, Leary M, Longacre M, Byler S, Lapinska K, Willbanks A, Sarkar S EMT and tumor metastasis.

Clin Transl Med Mittal V Epithelial mesenchymal transition in tumor metastasis. Annu Rev Pathol — Wang H, Unternaehrer JJ Epithelial-mesenchymal transition and cancer stem cells: at the crossroads of differentiation and dedifferentiation.

Dev Dyn — Nagarsheth N, Wicha MS, Zou W Chemokines in the cancer microenvironment and their relevance in cancer immunotherapy. Nat Rev Immunol Mol Med Rep — Liao Z, Chua D, Tan NS Reactive oxygen species: a volatile driver of field cancerization and metastasis. Miyazaki Y, Hara A, Kato K, Oyama T, Yamada Y, Mori H, Shibata T The effect of hypoxic microenvironment on matrix metalloproteinase expression in xenografts of human oral squamous cell carcinoma.

Int J Oncol — Zhang L, Huang G, Li X, Zhang Y, Jiang Y, Shen J, Liu J, Wang Q, Zhu J, Feng X Hypoxia induces epithelial-mesenchymal transition via activation of SNAI1 by hypoxia-inducible factor-1α in hepatocellular carcinoma.

BMC Cancer Nishida N, Kudo M Oxidative stress and epigenetic instability in human hepatocarcinogenesis. Dig Dis — Nishida N, Yano H, Nishida T, Kamura T, Kojiro MJ Angiogenesis in cancer.

Vasc Health Risk Manag Kim Y-W, Byzova TVJB Oxidative stress in angiogenesis and vascular disease. Blood — Carmeliet PJ VEGF as a key mediator of angiogenesis in cancer.

Oncology — Babior BM NADPH oxidase. Curr Opin Immunol — Xia C, Meng Q, Liu LZ, Rojanasakul Y, Wang XR, Jiang BH Reactive oxygen species regulate angiogenesis and tumor growth through vascular endothelial growth factor. Cancer Res — Sun X, Wei J, Tang Y, Wang B, Zhang Y, Shi L, Guo J, Hu F, Li X Leptin-induced migration and angiogenesis in rheumatoid arthritis is mediated by reactive oxygen species.

FEBS Open Bio — Coussens LM, Werb Z Inflammation and cancer. Nature Blaylock RL Cancer microenvironment, inflammation and cancer stem cells: a hypothesis for a paradigm change and new targets in cancer control. Surg Neurol Int Landskron G, De la Fuente M, Thuwajit P, Thuwajit C, Hermoso MA Chronic inflammation and cytokines in the tumor microenvironment.

J Immunol Res Hanahan D, Weinberg RA Hallmarks of cancer: the next generation. Kiraly O, Gong G, Olipitz W, Muthupalani S, Engelward BP Inflammation-induced cell proliferation potentiates DNA damage-induced mutations in vivo.

PLoS Genet e Mantovani A, Allavena P, Sica A, Balkwill F Cancer-related inflammation. Grivennikov SI, Greten FR, Karin M Immunity, inflammation, and cancer. Kim SS, Ruiz VE, Carroll JD, Moss SF Helicobacter pylori in the pathogenesis of gastric cancer and gastric lymphoma.

Wroblewski LE, Peek RM, Wilson KT Helicobacter pylori and gastric cancer: factors that modulate disease risk. Clin Microbiol Rev — Arbuthnot P, Kew M Hepatitis B virus and hepatocellular carcinoma.

Int J Exp Pathol — El-Serag HB Hepatocellular carcinoma and hepatitis C in the United States. Hepatology — de Martel C, Franceschi S Infections and cancer: established associations and new hypotheses. Crit Rev Oncol Hematol — Balkwill F, Mantovani A Inflammation and cancer: back to Virchow?

Lancet — Stark T, Livas L, Kyprianou N Inflammation in prostate cancer progression and therapeutic targeting.

Transl Androl Urol Shrihari T Dual role of inflammatory mediators in cancer. Ecancermedicalscience Hoesel B, Schmid JA The complexity of NF-κB signaling in inflammation and cancer. Mogensen TH Pathogen recognition and inflammatory signaling in innate immune defenses. Franchi L, Eigenbrod T, Muñoz-Planillo R, Nuñez G The inflammasome: a caspaseactivation platform that regulates immune responses and disease pathogenesis.

Nat Immunol — Fialkow L, Wang Y, Downey GP Reactive oxygen and nitrogen species as signaling molecules regulating neutrophil function. Salzano S, Checconi P, Hanschmann E-M, Lillig CH, Bowler LD, Chan P, Vaudry D, Mengozzi M, Coppo L, Sacre S Linkage of inflammation and oxidative stress via release of glutathionylated peroxiredoxin-2, which acts as a danger signal.

Proc Natl Acad Sci — PubMed CAS PubMed Central Google Scholar. Martinon F Signaling by ROS drives inflammasome activation. Eur J Immunol — Latz E, Xiao TS, Stutz A Activation and regulation of the inflammasomes. Nat Rev Immunol — Zhou R, Tardivel A, Thorens B, Choi I, Tschopp J Thioredoxin-interacting protein links oxidative stress to inflammasome activation.

Nat Immunol Zhou R, Yazdi AS, Menu P, Tschopp J A role for mitochondria in NLRP3 inflammasome activation. Nature — Ghezzi P Role of glutathione in immunity and inflammation in the lung. Int J Gen Med Morgan MJ, Liu Z-G Crosstalk of reactive oxygen species and NF-κB signaling.

Blanco P, Palucka AK, Pascual V, Banchereau J Dendritic cells and cytokines in human inflammatory and autoimmune diseases.

Cytokine Growth Factor Rev — Klampfer L Cytokines, inflammation and colon cancer. Curr Cancer Drug Targets — Liang M, Zhang P, Fu J Up-regulation of LOX-1 expression by TNF-α promotes trans-endothelial migration of MDA-MB breast cancer cells.

Zamarron BF, Chen W Dual roles of immune cells and their factors in cancer development and progression. Int J Biol Sci Lin W-W, Karin M A cytokine-mediated link between innate immunity, inflammation, and cancer. J Clin Investig Knüpfer H, Preiss R Serum interleukin-6 levels in colorectal cancer patients—a summary of published results.

Int J Colorectal Dis — Tanaka T, Bai Z, Srinoulprasert Y, Yang B, Hayasaka H, Miyasaka M Chemokines in tumor progression and metastasis. Cancer Sci — Yu JH, Kim H Oxidative stress and cytokines in the pathogenesis of pancreatic cancer.

J Cancer Prev Prawan A, Buranrat B, Kukongviriyapan U, Sripa B, Kukongviriyapan V Inflammatory cytokines suppress NAD P H: quinone oxidoreductase-1 and induce oxidative stress in cholangiocarcinoma cells.

J Cancer Res Clin Oncol — Oncol Rep — Esquivel-Velázquez M, Ostoa-Saloma P, Palacios-Arreola MI, Nava-Castro KE, Castro JI, Morales-Montor J The role of cytokines in breast cancer development and progression. J Interferon Cytokine Res — Wojdasiewicz P, Poniatowski ŁA, Szukiewicz D The role of inflammatory and anti-inflammatory cytokines in the pathogenesis of osteoarthritis.

Mediators Inflamm Ravichandran K, Tyagi A, Deep G, Agarwal C, Agarwal R Interleukininduced iNOS expression in human lung carcinoma A cells: involvement of STAT and MAPK pathways. Scheller J, Chalaris A, Schmidt-Arras D, Rose-John S The pro-and anti-inflammatory properties of the cytokine interleukin Biochim Biophys Acta Mol Cell Res — Brizzi MF, Formato L, Dentelli P, Rosso A, Pavan M, Garbarino G, Pegoraro M, Camussi G, Pegoraro L Interleukin-3 stimulates migration and proliferation of vascular smooth muscle cells.

Circulation — Ehrlich LA, Chung HY, Ghobrial I, Choi SJ, Morandi F, Colla S, Rizzoli V, Roodman GD, Giuliani N IL-3 is a potential inhibitor of osteoblast differentiation in multiple myeloma.

Gupta N, Barhanpurkar AP, Tomar GB, Srivastava RK, Kour S, Pote ST, Mishra GC, Wani MR IL-3 inhibits human osteoclastogenesis and bone resorption through downregulation of c-Fms and diverts the cells to dendritic cell lineage. J Immunol — Heikkilä K, Ebrahim S, Lawlor DA Systematic review of the association between circulating interleukin-6 IL-6 and cancer.

Eur J Cancer — Hodge DR, Hurt EM, Farrar WL The role of IL-6 and STAT3 in inflammation and canicer. Aggarwal BB, Sethi G, Ahn KS, Sandur SK, Pandey MK, Kunnumakkara AB, Sung B, Ichikawa H Targeting signal-transducer-and-activator-of-transcription-3 for prevention and therapy of cancer.

Rao V, Dyer C, Jameel J, Drew P, Greenman J Potential prognostic and therapeutic roles for cytokines in breast cancer. J Clin Oncol — Kinoshita H, Hirata Y, Nakagawa H, Sakamoto K, Hayakawa Y, Takahashi R, Nakata W, Sakitani K, Serizawa T, Hikiba Y Interleukin-6 mediates epithelial—stromal interactions and promotes gastric tumorigenesis.

PLoS One 8:e Gasche JA, Hoffmann J, Boland CR, Goel A Interleukin-6 promotes tumorigenesis by altering DNA methylation in oral cancer cells. Int J Cancer — Baffet G, Braciak T, Fletcher R, Gauldie J, Fey G, Northemann W Autocrine activity of interleukin 6 secreted by hepatocarcinoma cell lines.

Mol Biol Med — Atreya R, Mudter J, Finotto S, Müllberg J, Jostock T, Wirtz S, Schütz M, Bartsch B, Holtmann M, Becker C Blockade of interleukin 6 trans signaling suppresses T-cell resistance against apoptosis in chronic intestinal inflammation: evidence in crohn disease and experimental colitis in vivo.

Nat Med Becker C, Fantini MC, Schramm C, Lehr HA, Wirtz S, Nikolaev A, Burg J, Strand S, Kiesslich R, Huber S TGF-β suppresses tumor progression in colon cancer by inhibition of IL-6 trans-signaling. Immunity — McGeachy MJ, Bak-Jensen KS, Chen Y, Tato CM, Blumenschein W, McClanahan T, Cua DJ TGF-[beta] and IL-6 drive the production of IL and IL by T cells and restrain TH cell-mediated pathology.

Onishi RM, Gaffen SL Interleukin and its target genes: mechanisms of interleukin function in disease. Immunology — Drug Des Devel Ther Maniati E, Soper R, Hagemann T Up for Mischief?

Oncogene Infect Agent Cancer Numasaki M, Fukushi J-I, Ono M, Narula SK, Zavodny PJ, Kudo T, Robbins PD, Tahara H, Lotze MT Interleukin promotes angiogenesis and tumor growth. Kolls JK, Lindén A Interleukin family members and inflammation.

Kryczek I, Wei S, Zou L, Altuwaijri S, Szeliga W, Kolls J, Chang A, Zou W Cutting edge: Th17 and regulatory T cell dynamics and the regulation by IL-2 in the tumor microenvironment. Swann JB, Smyth MJ Immune surveillance of tumors.

Meier B, Radeke H, Selle S, Younes M, Sies H, Resch K, Habermehl G Human fibroblasts release reactive oxygen species in response to interleukin-1 or tumour necrosis factor-α. Biochem J — Li Q, Engelhardt JF Interleukin-1β induction of NFκB is partially regulated by H2O2-mediated activation of NFκB-inducing kinase.

J Biol Chem — Hsu S, Hsu P Autocrine and paracrine functions of cytokines in malignant lymphomas. Biomed Pharmacother — Endocrinology — Yuzhalin A, Kutikhin A Interleukins in cancer biology: their heterogeneous role.

Academic, Cambridge. Szlosarek P, Charles KA, Balkwill FR Tumour necrosis factor-α as a tumour promoter. Szlosarek PW, Balkwill FR Tumour necrosis factor α: a potential target for the therapy of solid tumours.

Lancet Oncol — Leek R, Landers R, Fox S, Ng F, Harris A, Lewis C Association of tumour necrosis factor alpha and its receptors with thymidine phosphorylase expression in invasive breast carcinoma.

Br J Cancer Sethi G, Sung B, Aggarwal BB TNF: a master switch for inflammation to cancer. Dempsey PW, Doyle SE, He JQ, Cheng G The signaling adaptors and pathways activated by TNF superfamily. Aggarwal BB Signalling pathways of the TNF superfamily: a double-edged sword.

Aggarwal BB, Shishodia S, Ashikawa K, Bharti AC The role of TNF and its family members in inflammation and cancer: lessons from gene deletion. Curr Drug Targets Inflamm Allergy — Wajant H, Pfizenmaier K, Scheurich P Tumor necrosis factor signaling. Cell Death Differ Wang X, Lin Y Tumor necrosis factor and cancer, buddies or foes?

Acta Pharmacol Sin — Devin A, Cook A, Lin Y, Rodriguez Y, Kelliher M, Liu Z-G The distinct roles of TRAF2 and RIP in IKK activation by TNF-R1: TRAF2 recruits IKK to TNF-R1 while RIP mediates IKK activation. Yang J, Lin Y, Guo Z, Cheng J, Huang J, Deng L, Liao W, Chen Z, Zheng-gang L, Su B The essential role of MEKK3 in TNF-induced NF-[kappa] B activation.

Karin M, Yamamoto Y, Wang QM The IKK NF-[kappa] B system: a treasure trove for drug development. Nat Rev Drug Discov Kamata H, Honda S-I, Maeda S, Chang L, Hirata H, Karin M Reactive oxygen species promote TNFα-induced death and sustained JNK activation by inhibiting MAP kinase phosphatases.

The derivatives were more stable than natural juglone and less susceptible to oxidation, preserving the antitumoral activity. Derivatives with allyl or butyl substitution were most effective, inhibiting the proliferation and inducing apoptosis of glioma cells mediated by ROS.

This Research Topic also includes the important work of Tang et al. Under another approach, the authors demonstrated that the hepatoxicity of Sunitinib, a multi-targeted tyrosine kinase inhibitor with remarkable anticancer activity, may be protected by glycyrrhetinic acid.

Sunitinib reduced the viability of nontumoral hepatocytes mediated by the activation of mitogen-activated proteins kinases MAPKs due to the exacerbation of ROS production. The apoptosis and autophagy induced by Sunitib were relieved by the treatment with glycyrrhetinic acid.

According to the authors, glycyrrhetinic acid could be a preventive therapy to reduce liver injury caused by Sunitinib. In a study characterized by a robust experimental design, Rahimifard et al.

Furthermore, the treatment suppressed telomerase activity, pro-inflammatory gene expression, and cell invasion. These findings highlight the potential clinical utility of cisplatin-resveratrol combination in the management of cancer.

This area of research also encompasses the important contributions made by Liu et al. Platinum-based chemotherapy induces cancer cell death by elevating oxidative stress levels to a cytotoxic extent.

Liu et al. have identified a noteworthy association between the CAT rs polymorphism and platinum-based chemotherapy-related progression-free survival in patients with lung cancer, indicating its potential as a prognostic biomarker for such patients.

A pioneering review by Li et al. has uncovered the importance of ROS in regulating multiple signaling pathways. Cancer cells can resist therapy by increasing their antioxidant defense system to cope with high levels of ROS. The authors summarized the molecular mechanisms behind this resistance, including drug efflux, DNA repair, stemness maintenance and tumor microenvironment alteration.

Zhuo et al. They demonstrated that the oncogene eIF3a plays a crucial role in cancer development and responses to various therapies, especially those known to promote oxidative stress.

Using a proteomics approach, they systematically elucidated its relationship with oxidative stress and found that it is involved in lipid peroxidation, which affects the response of cancer cells to cytotoxic antitumor drugs. These findings suggest that eIF3a may serve as a bridge between oxidative stress and cancer, providing insights into cancer development and therapy from cellular processes, molecular signaling pathways, metabolism, and immune responses.

All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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