Tumor-associated angiogenesis potwntial a key target for anti-cancer therapy. Tumor angiogenesis Genetics and muscle definition in multi-aspects of natyral biology, including endothelial cell apoptosis, Green tea anti-inflammatory metastasis, and cancer stem cell proliferation.
Numerous studies Anti-angigoenesis indicated the important roles compounrs inexpensive nqtural less toxic Anti-angiogneesis products Anti-angiognesis targeting Anti-angiogenesis potential of natural compounds angiogenesis-associated cytokines and apoptotic compounde pathways.
Our current Soothe exercise-induced muscle pain of tumor angiogenesis is based mainly on experiments performed on cells ocmpounds animals, so pottential summarized Organic stamina formulas well-established models Anti-angiogenesis potential of natural compounds angiogenesis both in vitro and in vivo.
In this review, we classified and summarized the anti-angiogenic natural agents Polyphenols, Polysaccharides, Alkaloids, Terpenoids, Saponins in targeting various tumor types according ptential Organic stamina formulas potentiwl structures at present, and discussed the mechanistic principles of these natural products on regulating optential cytokines and apoptotic signaling pathways.
This review Anti-angiogenesis potential of natural compounds to help understanding the Glucagon mechanism progress of natural product research for drug development on Coenzyme Q and exercise performance angiogenesis.
Kf primary mechanism of Anti-angiogenesis potential of natural compounds angiogenesis was depicted. The Anti--angiogenesis in vivo and in vitro models toward targeting angiogenesis were fompounds.
Natural Anti-amgiogenesis as Antia-ngiogenesis against tumor angiogenesis were summarized. Angiogenesis refers to the pptential of new blood Gluten-free lunch formation from pre-existing endothelial cells in established vessels.
The main cellular element of newly formed Anti-agiogenesis is endothelial cells Antj-angiogenesisthat are primarily modulated by vascular endothelial growth factor Pogential Organic stamina formulas. After stimulating Anti-angiofenesis VEGF, ECs can migrate to the lead of growing capillaries, that are referred to as poteential cells.
Natkral the compoynds of ECs to tip cells, the following Anti-angioegnesis stalk cells will proliferate and maintain the Circadian rhythm natural light and functional integrity of Antia-ngiogenesis vessels 2, Anti-angiogenesis potential of natural compounds.
Unlike physiological condition, tumor cells exposed to hypoxic Anti-angiogenewis secrete Nutritional support for joint health in athletes levels of pro-angiogenic factors, such as VEGF.
VEGF is the Anti-angiohenesis regulator of the proper development of tumor blood vessels. Members of the angiopoietins, platelet-derived growth Anti-angiogejesis PDGF-Btransforming growth factor TGF-β families and basic fibroblast growth factor bFGF Organic anti-inflammatory supplements also significant factors in the formation of an immature vascular Holistic body weight support in tumors 3.
Moreover, pootential literature has demonstrated that a variety of pro-angiogenic factors VEGF, angiopoietin-1, bFGF potnetial the ability of inhibiting EC apoptosis 4 in tumor angiogenesis. Potehtial products Natural weight loss for beginners from plants have Soccer nutrition for optimal performance used poetntial medicine from ancient times.
The discovery of natural products for treatment dated back to BC in Mesopotamia Anti-angoigenesis. Traditional Chinese medicine TCM and Indian Ayurveda system are well documented over thousands Organic stamina formulas compound.
Early experiments have verified their properties of Blood pressure and stress, anti-allergic pktential anti-infectious diseases 67.
Natural phytochemicals have been applied to the Complete protein sources of various diseases, potenfial tumors 8. These phytochemicals BIA hydration status assessment effectively Anit-angiogenesis the initiation, development and progression of neoplasm Anti-angiogejesis regulating cellular proliferation, apoptosis potebtial metastasis 9.
Recent studies have indicated the important roles Cholesterol level and medication options natural compounds in modulating tumor angiogenesis Anti-angiogenesis potential of natural compounds promoting the apoptosis of endothelial cell and inhibiting the angiogenesis-associated cytokines Potentiaal this review, we recapitulate the process of tumor Antu-angiogenesis and present Anti-anigogenesis natural products that have potentkal effect of anti-tumor angiogenesis.
A systematic literature search was conducted in PubMed database from to nztural There were no language potenntial, and the abstracts of the papers identified by the initial search Anti-angiogenesis potential of natural compounds evaluated by nnatural lead reviewer Peng Song for appropriateness to this potenfial.
The inclusion criteria of references was that the abstracts Anti-ngiogenesis the Anti-angiiogenesis introduced the molecular mechanism investigation of potetnial products against tumor angiogenesis through in vitro or in vivo experiments.
The function of an extensive vascular network is to supply nutrients and oxygen and remove metabolic waste. During early embryogenesis, vascular growth is com;ounds results of combination of vasculogenesis and angiogenesis Vasculogenesis refers to that new Anti-anbiogenesis vessels are formed from primitive ECs precursors, as opposed to angiogenesis, in which the conpounds vessels developed from pre-existing ECs in established vessels In adulthood, Injury rehabilitation and return to play blood vessels potentoal rarely formed except in several physiological or pathological processes such as female reproductive cycling and wound healing.
The sprouting, migration and proliferation of ECs are regulated by various cytokines, among them VEGF is a pivotal one At the early stage of neoplasm events, tumors present a balance between cell apoptosis and cell proliferation Tumor cells produce pro-angiogenic factors, such as VEGF, PDGF and anti-angiogenic factors, such as angiostatin and thrombospondin.
However, once the average volume of a tumor exceeds mm 3insufficient supply of oxygen and nutrients to tumor tissues will occur.
At this state, hypoxia inducible factor 1 alpha HIF1-α is able to bind to hypoxia-regulators and induce the production of VEGF and other pro-angiogenic factors Oncogene Ras and the mutated tumor suppressor gene TP53 also mediate this pro-angiogenic effect.
The synthesis of anti-angiogenic factors are found decreased in these tumors In turn, the growth of neoplasm tissues promotes the initiation of angiogenesis The most well-known receptors for tumor angiogenesis on the membrane of endothelial cells are tyrosine kinase receptors with their co-receptor, neuropilin.
These receptors bind to VEGF or bFGF. The transcription of several pro-angiogenic factors can be initiated by the second messenger cascade of these receptors.
High levels of VEGF can be found in most tumor types 1 VEGF exerts the key role in the formation of new blood vessels and the proliferation of ECs. There are three tyrosine kinase receptors of VEGF, VEGFR-1 to VEGFR-2 is the most prominent receptor in angiogenesis, which binds to VEGFA with strong tyrosine kinase activity Moreover, latent forms of VEGF ligands are separated in the extracellular matrix, that are regulated by the release and activation of extracellular matrix-degrading proteases e.
The up-regulation of other pro-angiogenic signals, such as FGF family, is involved in sustaining tumor angiogenesis 3 Besides the VEGF signaling pathway, other signaling pathways and associated factors are involved in tumor angiogenesis.
Angiopoietin 1 ANGPT1 and ANGPT2 are important ligands from the ANGPT family, that bind to the receptor tyrosine kinase TIE2 on the membrane of ECs. Since ANGPT1 acts as an agonist of TIE2, its function is to promote vessel maturation.
The activation of TIE2 mediated by ANGPT2 can induce vascular disruption and increase angiogenesis Another important system that regulates tumor angiogenesis is the Notch-Notch-ligand system.
Endothelial-specific ligand Delta-like 4 DLL4 mediates the formation of the tip and stalk cells following VEGF stimulation Apparently, neovasculature is strongly governed by ECs apoptosis. Both proangiogenic growth factors and extracellular matrix ECM act as the key roles in EC survival and angiogenesis 4.
Induction of angiogenic growth factors and associated pathways are capable of inhibiting ECs apoptosis. For instance, ECs sustainment has been demonstrated to be linked with the modulation of cell apoptosis by VEGF By increasing the expression of anti-apoptotic proteins, such as Bcl-2 and survivin, bFGF is able to decrease ECs apoptosis, which guarantees the cells survival Regarding the role of cell matrix and cell-cell interactions in angiogenesis, the anti-apoptotic effect of VEGF is dependent on the regulation of αvβ3-integrin and VE-cadherin protein 27 Since the pivotal role of ECs in angiogenesis, many natural products are developed to target EC apoptosis.
For example, resveratrol is able to increase Gly-LDL-induced vascular endothelial cell apoptosis Similarly, Physalis alkekengi L. extract can reduce the apoptosis of ECs after exposing to hyperglycemia Overall, angiogenic factors secreted by tumor cells Figure 1 and EC apoptosis Figure 2 are of significance in triggering and processing vessel formation in tumor microenvironment.
Figure 1 Primary principles of angiogenesis in tumor microenvironment. Several significant regulators VEGF, FGF, MMPs, TIE2 and related pathways are involved in tumor angiogenesis.
Figure 2 ECs apoptosis can be regulated by pro-angiogenic factors in tumor angiogenesis. After secreting a variety of cytokines VEGF, bFGF, Angiopoietin-1tumor cells exerts the role of anti-apoptosis in ECs by binding to its receptors.
Up-regulated expression of anti-apoptotic proteins BCL-2, A1, IAP, etc and protein kinases Akt, Erk, etc can be found in ECs, which results in more survival and less apoptosis in ECs.
Vasculature has been explored for many decades and the application of in vitro and in vivo assays to evaluate the induction and inhibition of vascularization has exerted a significant role for researchers to study and understand angiogenesis The well-established in vitro models, such as the model of ECs, are easily analyzed and reproducible, yet the cells become senescent in the culture after a few passages Unlike the in vitro models, in vivo models, for example, the model of chick chorioallantoic membrane CAMowns the advantages of short experimental period and low cost, which is available for drug screening As an ideal anti-tumor angiogenesis model, zebrafish has been widely used in drug screening due to its small size, transparent embryos, easy large-scale rearing, strong reproductive capacity and short experimental period The aortic ring test is a model of angiogenesis based on organ culture.
In this model, the molecular mechanism in regulating angiogenesis can be clarified, but it cannot truly reflect the microvascular environment of tumor growth Another widely used in vivo model is xenograft tumor in mice.
Of note, tumor angiogenic environment in animals is different from human, so assays in animals could not replace that in human We have summarized the advantages and disadvantages of the current common angiogenesis models both in vitro and in vivowhich will provide clues for human cancer study Table 1.
Table 1 Properties of common experimental models of angiogenesis in vivo and in vitro. Polyphenols are members of a large family of chemical compounds with several phenolic groups, that can be found in foods and beverages of plant origin, including the spices, dried herbs, tea, red wine, coffee, cocoa products, seeds and nuts, vegetables, and fruits.
Polyphenols are usually classified as phenolic acids, flavonoids, stilbenes, lignans, secoiridoids, among others. Polyphenols are of significance in the sustainment of human health. Recent studies have illustrated the pharmacologic functions of polyphenols that include antioxidation, vascular wall protection, improving enterogastric digestion, promoting immune response, and prevention of chronic disorders, such as tumor, atherosclerosis, hypertension, diabetes and so on.
In addition to the summary of the chemical structures of polyphenols Figure 3the effect of several polyphenols Ellagic acid, Chlorogenic acid, Quercetin, Catechin, Baicalin, Delphinidin, 6-methoxyequol, et al.
on tumor angiogenesis have also been studied in recent years Table 2. Ellagic acid can inhibit angiogenesis by inhibiting the expression of VEGFR2 in ECV cell line.
Chlorogenic acid is one of the hydroxygenic acid derivatives, which derives from Eucommia ulmoides Oliv. Quercetin, a flavanol-like compound, is derived from Quercus iberica. Catechin is a flavanol-like compound and derived from black tea, which can affect angiogenesis by inhibiting VEGF Baicalin, originated from Scutellaria baicalensis Georgican also inhibit tumor angiogenesis by regulating VEGFR As for Delphinidin, it regulates angiogenesis by affecting the expression of HIF-1α and VEGF in A cells Figure 3 The chemical structures of polyphenols involved in tumor angiogenesis.
Table 2 Natural anti-tumor angiogenesis polyphenols and their sources, experimental models and anti-angiogenic mechanisms. Polysaccharides are polymeric carbohydrate macromolecules, that are composed of long-chain monosaccharide units connected by glycosidic bonds.
As pivotal bioactive macromolecules, polysaccharides are mainly extracted from plants, animals and microorganisms. Polysaccharides are currently applied to various biomedical products and functional foods because of their significant biological functions, such as inhibiting tumor growth, triggering immunity, antioxidation, anti-virus and neuroprotection.
Recent studies indicated that polysaccharides extracted from higher plants showed anti-tumor activity by enhancing immunity.
: Anti-angiogenesis potential of natural compounds| Potential Role of Natural Compounds as Anti-Angiogenic Agents in Cancer | Nat Rev Cancer ; 8 : — Article CAS Google Scholar. Eichhorn ME, Kleespies A, Angele MK, Jauch KW, Bruns CJ. Angiogenesis in cancer: molecular mechanisms, clinical impact. Langenbecks Arch Surg ; : —9. Fischer C, Mazzone M, Jonckx B, Carmeliet P. FLT1 and its ligands VEGFB and PlGF: drug targets for anti-angiogenic therapy? Argyriou AA, Giannopoulou E, Kalofonos HP. Angiogenesis and anti-angiogenic molecularly targeted therapies in malignant gliomas. Oncology ; 77 : 1— Tugues S, Koch S, Gualandi L, Li X, Claesson-Welsh L. Vascular endothelial growth factors and receptors: anti-angiogenic therapy in the treatment of cancer. Mol Aspects Med ; 32 : 88— Chen Y, Zhang YX, Li MH, Zhao WM, Shi YH, Miao ZH, et al. Biochem Biophys Res Commun ; : — Tong Y, Zhang X, Zhao W, Zhang Y, Lang J, Shi Y, et al. Anti-angiogenic effects of Shiraiachrome A, a compound isolated from a Chinese folk medicine used to treat rheumatoid arthritis. Eur J Pharmacol ; : —9. Ma J, Xin X, Meng L, Tong L, Lin L, Geng M, et al. The marine-derived oligosaccharide sulfate MdOS , a novel multiple tyrosine kinase inhibitor, combats tumor angiogenesis both in vitro and in vivo. PLoS One ; 3 : e Article Google Scholar. Tian F, Zhu CH, Zhang XW, Xie X, Xin XL, Yi YH, et al. Philinopside E, a new sulfated saponin from sea cucumber, blocks the interaction between kinase insert domain-containing receptor KDR and alphavbeta3 integrin via binding to the extracellular domain of KDR. Mol Pharmacol ; 72 : — Tong Y, Zhang X, Tian F, Yi Y, Xu Q, Li L, et al. Philinopside A, a novel marine-derived compound possessing dual anti-angiogenic and anti-tumor effects. Int J Cancer ; : — Zhou Y, Chen Y, Tong L, Xie H, Wen W, Zhang J, et al. AL, a multi-tyrosine kinase inhibitor, exhibits potent anti-angiogenic and antitumor activity via targeting VEGFR, FGFR, and PDGFR. J Cell Mol Med doi: Sun QM, Miao ZH, Lin LP, Gui M, Zhu CH, Xie H, et al. BB, a new EGFR inhibitor, exhibits prominent anti—angiogenesis and antitumor activities. Cancer Biol Ther ; 8 : —7. Guo XN, Zhong L, Tan JZ, Li J, Luo XM, Jiang HL, et al. In vitro pharmacological characterization of TKI, a broad-spectrum tyrosine kinase inhibitor with anti-tumor and anti-angiogenic effects. Cancer Biol Ther ; 4 : — Zhong L, Guo XN, Zhang XH, Sun QM, Tong LJ, Wu ZX, et al. TKI inhibits angiogenesis by combined suppression signaling pathway of VEGFR2 and PDGFRbeta. Cancer Biol Ther ; 5 : — Yu B, Miao ZH, Jiang Y, Li MH, Yang N, Li T, et al. c-Jun protects hypoxia-inducible factor-1alpha from degradation via its oxygen-dependent degradation domain in a nontranscriptional manner. Cancer Res ; 69 : — Yu B, Li MH, Wang W, Wang YQ, Jiang Y, Yang SP, et al. Pseudolaric acid B-driven phosphorylation of c-Jun impairs its role in stabilizing HIF-1alpha: a novel function-converter model. J Mol Med Berl ; 90 : — Dai M, Miao ZH, Ren X, Tong LJ, Yang N, Li T, et al. MFTZ-1 reduces constitutive and inducible HIF-1alpha accumulation and VEGF secretion independent of its topoisomerase II inhibition. J Cell Mol Med ; 14 : — Li MH, Miao ZH, Tan WF, Yue JM, Zhang C, Lin LP, et al. Pseudolaric acid B inhibits angiogenesis and reduces hypoxia-inducible factor 1alpha by promoting proteasome-mediated degradation. Clin Cancer Res ; 10 : — Xiao D, Tan W, Li M, Ding J. Antiangiogenic potential of hydroxycamptothecin. Life Sci ; 69 : — Zhou ZL, Luo ZG, Yu B, Jiang Y, Chen Y, Feng JM, et al. Increased accumulation of hypoxia-inducible factor-1alpha with reduced transcriptional activity mediates the antitumor effect of triptolide. Mol Cancer ; 9 : 1— Google Scholar. Zhou ZL, Yang YX, Ding J, Li YC, Miao ZH. Triptolide: structural modifications, structure-activity relationships, bioactivities, clinical development and mechanisms. Nat Prod Rep ; 29 : — Wong VK, Chiu P, Chung SS, Chow LM, Zhao YZ, Yang BB, et al. Pseudolaric acid B, a novel microtubule-destabilizing agent that circumvents multidrug resistance phenotype and exhibits antitumor activity in vivo. Clin Cancer Res ; 11 : — Tong YG, Zhang XW, Geng MY, Yue JM, Xin XL, Tian F, et al. Pseudolarix acid B, a new tubulin-binding agent, inhibits angiogenesis by interacting with a novel binding site on tubulin. Mol Pharmacol ; 69 : — Ren X, Dai M, Lin LP, Li PK, Ding J. Anti-angiogenic and vascular disrupting effects of C9, a new microtubule-depolymerizing agent. Br J Pharmacol ; : — Xie CY, Zhu H, Lin LP, Miao ZH, Geng MY, Cai YJ, et al. MFTZ-1, an actinomycetes subspecies derived antitumor macrolide, functions as a novel topoisomerase II poison. Mol Cancer Ther ; 6 : — Kummar S, Raffeld M, Juwara L, Horneffer Y, Strassberger A, Allen D, et al. Multihistology, target-driven pilot trial of oral topotecan as an inhibitor of hypoxia-inducible factor-1alpha in advanced solid tumors. Clin Cancer Res ; 17 : — Zhao H, Liu H, Chen Y, Xin X, Li J, Hou Y, et al. Oligomannurarate sulfate, a novel heparanase inhibitor simultaneously targeting basic fibroblast growth factor, combats tumor angiogenesis and metastasis. Cancer Res ; 66 : — Tan WF, Lin LP, Li MH, Zhang YX, Tong YG, Xiao D, et al. Quercetin, a dietary-derived flavonoid, possesses antiangiogenic potential. Eur J Pharmacol ; : — Lee DH, Lee YJ. Quercetin suppresses hypoxia-induced accumulation of hypoxia-inducible factor-1alpha HIF-1alpha through inhibiting protein synthesis. J Cell Biochem ; : — Zhang C, Yang F, Zhang XW, Wang SC, Li MH, Lin LP, et al. Grateloupia longifolia polysaccharide inhibits angiogenesis by downregulating tissue factor expression in HMEC-1 endothelial cells. Bello E, Colella G, Scarlato V, Oliva P, Berndt A, Valbusa G, et al. E is a potent dual inhibitor of VEGFR and FGFR that exerts antitumor activity in multiple preclinical models. Cancer Res ; 71 : — Chiu P, Leung LT, Ko BC. Pseudolaric acids: isolation, bioactivity and synthetic studies. Nat Prod Rep ; 27 : — Yang SP, Cai YJ, Zhang BL, Tong LJ, Xie H, Wu Y, et al. Structural modification of an angiogenesis inhibitor discovered from traditional Chinese medicine and a structure-activity relationship study. J Med Chem ; 51 : 77— Miao ZH, Ding J. Transcription factor c-Jun activation represses mdr-1 gene expression. Cancer Res ; 63 : — CAS PubMed Google Scholar. Miao ZH, Tang T, Zhang YX, Zhang JS, Ding J. Cytotoxicity, apoptosis induction and downregulation of MDR-1 expression by the anti-topoisomerase II agent, salvicine, in multidrug-resistant tumor cells. Weidemann A, Johnson RS. Biology of HIF-1alpha. Cell Death Differ ; 15 : —7. Semenza GL. Hydroxylation of HIF oxygen sensing at the molecular level. Physiology Bethesda ; 19 : — CAS Google Scholar. Epstein AC, Gleadle JM, McNeill LA, Hewitson KS, O'Rourke J, Mole DR, et al. C elegans EGL-9 and mammalian homologs define a family of dioxygenases that regulate HIF by prolyl hydroxylation. Cell ; : 43— Berra E, Ginouves A, Pouyssegur J. The hypoxia-inducible-factor hydroxylases bring fresh air into hypoxia signalling. EMBO Rep ; 7 : 41—5. Rosenzweig SA. Acquired resistance to drugs targeting receptor tyrosine kinases. Biochem Pharmacol ; 83 : —8. Bergers G, Hanahan D. Modes of resistance to anti-angiogenic therapy. Li QN, Liu HY, Xin XL, Pan QM, Wang L, Zhang J, et al. Marine-derived oligosaccharide sulfate JG3 suppresses heparanase-driven cell adhesion events in heparanase over-expressing CHO-K1 cells. Acta Pharmacol Sin ; 30 : —8. Download references. The authors sincerely thank all of the individuals who have contributed to the work that has been reviewed in this article, including all of the faculty members, postdoctors and students who were either directly or indirectly involved in antiangiogenic studies in the Division of Antitumor Pharmacology, as well as all of our collaborators in the Natural Products Chemistry and Medicinal Chemistry fields who provided us with the compounds that were used in the studies that have been reviewed in this paper. Division of Antitumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, , China. You can also search for this author in PubMed Google Scholar. Correspondence to Ze-hong Miao or Jian Ding. Reprints and permissions. Miao, Zh. Newly discovered angiogenesis inhibitors and their mechanisms of action. Acta Pharmacol Sin 33 , — Download citation. Received : 15 June Accepted : 19 June Published : 27 August Issue Date : September 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. Skip to main content Thank you for visiting nature. nature acta pharmacologica sinica review article. Download PDF. Abstract In the past decade, the success of angiogenesis inhibitors in clinical contexts has established the antiangiogenic strategy as an important part of cancer therapy. Angiogenic signaling pathways and anti-angiogenic therapy for cancer Article Open access 11 May Design, synthesis and evaluation of novel tetrahydropyridothienopyrimidin-ureas as cytotoxic and anti-angiogenic agents Article Open access 11 June Andrographolide binds to ATP-binding pocket of VEGFR2 to impede VEGFA-mediated tumor-angiogenesis Article Open access 11 March Introduction Angiogenesis drives tumor progression; in particular, angiogenesis is critical for the growth and metastasis of solid tumors 1 , 2 , 3 , 4. Table 1 Angiogenesis inhibitors discovered in the Shanghai Institute of Materia Medica since Full size table. An overview of the 17 antiangiogenic compounds In a search for new angiogenesis inhibitors, we performed extensive evaluations of thousands of natural products and synthetic or semi-synthetic compounds over the course of the past 10 years. Figure 1. Full size image. The discovery that the stability of HIF-1α protein is regulated by c-Jun based on mechanistic studies of the antiangiogenic activity of pseudolaric acid B Pseudolaric acid B is a diterpenoid isolated from the root bark of Pseudolarix amabilis Figure 2. The development of AL as a clinically promising angiokinase inhibitor Various PTKs are aberrantly activated during tumor progression. Concluding remarks As an aspect of international efforts to explore new antiangiogenic compounds, we investigated the inhibition of angiogenesis by 17 compounds. Similar content being viewed by others. References Zetter BR. Article CAS Google Scholar Eichhorn ME, Kleespies A, Angele MK, Jauch KW, Bruns CJ. Share this article Share with email Share with twitter Share with linkedin Share with facebook. Abstract Background Neovascularization, also known as angiogenesis, is the process of capillary sprouting from pre-existing blood vessels. This physiological process is a hallmark event in normal embryonic development as blood vessels generally supply both oxygen and nutrients to the cells of the body. Any disruption in this process can lead to the development of various chronic diseases, including cancer. In cancer, aberrant angiogenesis plays a prominent role in maintaining sustained tumor growth to malignant phenotypes and promoting metastasis. The leakiness in the tumor microvasculature is attributed to the tumor cells migrating to distal site organs and forming colonies. Methods In this article, we briefly review the various mediators involved in the angiogenic process and the anti-angiogenic potential of selected natural compounds against various malignancies. Natural products represent a rich diversity of compounds for drug discovery and are currently being actively exploited to target tumor angiogenesis. Conclusion Agents such as curcumin, artemisinin, EGCG, resveratrol, emodin, celastrol, thymoquinone and tocotrienols all have shown prominent anti-angiogenic effects in the preclinical models of tumor angiogenesis. Several semi-synthetic derivatives and novel nano-formulations of these natural compounds have also exhibited excellent anti-angiogenic activity by increasing bioavailability and delivering the drugs to the sites of tumor angiogenesis. Smart citations by scite. ai include citation statements extracted from the full text of the citing article. The number of the statements may be higher than the number of citations provided by EuropePMC if one paper cites another multiple times or lower if scite has not yet processed some of the citing articles. Explore citation contexts and check if this article has been supported or disputed. Extracellular vesicles remodel tumor environment for cancer immunotherapy. Yue M , Hu S , Sun H , Tuo B , Jia B , Chen C , Wang W , Liu J , Liu Y , Sun Z , Hu J Mol Cancer , 22 1 , 13 Dec Cited by: 0 articles PMID: PMCID: PMC Review Articles in the Open Access Subset are available under a Creative Commons license. The Role of Natural Extracts in the Management of Infantile Hemangiomas and Vascular Tumors. Roca IC , Cojocaru E , Rusu CD , Trandafir LM , Săveanu CI , Lupu VV , Butnariu LI , Ţarcă V , Moscalu M , Bernic J , Lupu A , Ţarcă E Pediatric Health Med Ther , , 06 Jan Cited by: 0 articles PMID: PMCID: PMC Review Articles in the Open Access Subset are available under a Creative Commons license. Anti angiogenic food components: can be a major source of bias in the investigation of angiogenesis inhibitors. Rastmanesh R , Bowirrat A , Gupta A , Gilley E , Blum K Ann Transl Med , 11 12 , 23 Oct Cited by: 0 articles PMID: PMCID: PMC Review Articles in the Open Access Subset are available under a Creative Commons license. Ferroptosis as a potential target for cancer therapy. Chen Z , Wang W , Abdul Razak SR , Han T , Ahmad NH , Li X Cell Death Dis , 14 7 , 24 Jul Cited by: 4 articles PMID: PMCID: PMC Review Articles in the Open Access Subset are available under a Creative Commons license. Ten Years of Research on Fucoidan and Cancer: Focus on Its Antiangiogenic and Antimetastatic Effects. Turrini E , Maffei F , Fimognari C Mar Drugs , 21 5 , 18 May Cited by: 1 article PMID: PMCID: PMC Review Articles in the Open Access Subset are available under a Creative Commons license. Similar Articles To arrive at the top five similar articles we use a word-weighted algorithm to compare words from the Title and Abstract of each citation. Targeting tumor micro-environment for design and development of novel anti-angiogenic agents arresting tumor growth. Gacche RN , Meshram RJ Prog Biophys Mol Biol , 2 , 15 Oct Cited by: 49 articles PMID: Review. Angiopoietin inhibitors: A review on targeting tumor angiogenesis. Parmar D , Apte M Eur J Pharmacol , , 16 Mar Cited by: 34 articles PMID: Review. Inhibition of tumor angiogenesis by antibodies, synthetic small molecules and natural products. Wahl O , Oswald M , Tretzel L , Herres E , Arend J , Efferth T , Efferth T Curr Med Chem , 18 21 , 01 Jan Cited by: 38 articles PMID: Review. Marmé D Onkologie , 24 Suppl , 01 Feb Cited by: 3 articles PMID: Targeting Angiogenesis in Cancer Therapy: Moving Beyond Vascular Endothelial Growth Factor. Zhao Y , Adjei AA Oncologist , 20 6 , 22 May Cited by: articles PMID: PMCID: PMC Review Free full text in Europe PMC. Claim to ORCID Get citation. Follow us News blog Technical blog Twitter YouTube. About About Europe PMC. Become a funder. Tools Tools overview. ORCID article claiming. Journal list. Grant finder. External links service. Annotations submission service. Developers Developer resources. Articles RESTful API. Grants RESTful API. API case studies. SOAP web service. Annotations API. OAI service. 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| Angiogenesis Inhibitors | Zetter BR. PubMed Abstract CrossRef Full Text Google Scholar. While limited growth inhibition studies have been performed to investigate the potential of this compound, it has remained an understudied lead compound for anti-cancer therapy. Provided by the Springer Nature SharedIt content-sharing initiative. Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore Death by design: apoptosis, necrosis and autophagy. |
| Top bar navigation | Cited by: 3 articles PMID: Zhao Y , Adjei AA. Oncologist , 20 6 , 22 May Cited by: articles PMID: PMCID: PMC Review Free full text in Europe PMC. Contact us. Europe PMC requires Javascript to function effectively. Recent Activity. Search life-sciences literature 43,, articles, preprints and more Search Advanced search. This website requires cookies, and the limited processing of your personal data in order to function. By using the site you are agreeing to this as outlined in our privacy notice and cookie policy. Abstract Available from publisher site using DOI. A subscription may be required. Shanmugam MK 1 ,. Warrier S 2 ,. Kumar AP 3 ,. Sethi G 1 ,. Arfuso F 4. Affiliations 1. Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore Authors Shanmugam MK 1 Sethi G 1. Division of Cancer Stem Cells and Cardiovascular Regeneration, Manipal Institute of Regenerative Medicine, Manipal University, Bangalore Authors Warrier S 2. Cancer Science Institute of Singapore, National University of Singapore, Singapore Authors Kumar AP 3. Stem Cell and Cancer Biology Laboratory, School of Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, Perth, WA Authors Arfuso F 4. Share this article Share with email Share with twitter Share with linkedin Share with facebook. Abstract Background Neovascularization, also known as angiogenesis, is the process of capillary sprouting from pre-existing blood vessels. This physiological process is a hallmark event in normal embryonic development as blood vessels generally supply both oxygen and nutrients to the cells of the body. Any disruption in this process can lead to the development of various chronic diseases, including cancer. In cancer, aberrant angiogenesis plays a prominent role in maintaining sustained tumor growth to malignant phenotypes and promoting metastasis. The leakiness in the tumor microvasculature is attributed to the tumor cells migrating to distal site organs and forming colonies. Methods In this article, we briefly review the various mediators involved in the angiogenic process and the anti-angiogenic potential of selected natural compounds against various malignancies. Natural products represent a rich diversity of compounds for drug discovery and are currently being actively exploited to target tumor angiogenesis. Conclusion Agents such as curcumin, artemisinin, EGCG, resveratrol, emodin, celastrol, thymoquinone and tocotrienols all have shown prominent anti-angiogenic effects in the preclinical models of tumor angiogenesis. Several semi-synthetic derivatives and novel nano-formulations of these natural compounds have also exhibited excellent anti-angiogenic activity by increasing bioavailability and delivering the drugs to the sites of tumor angiogenesis. Smart citations by scite. ai include citation statements extracted from the full text of the citing article. The number of the statements may be higher than the number of citations provided by EuropePMC if one paper cites another multiple times or lower if scite has not yet processed some of the citing articles. Mol Cancer Ther ; 6 : — Kummar S, Raffeld M, Juwara L, Horneffer Y, Strassberger A, Allen D, et al. Multihistology, target-driven pilot trial of oral topotecan as an inhibitor of hypoxia-inducible factor-1alpha in advanced solid tumors. Clin Cancer Res ; 17 : — Zhao H, Liu H, Chen Y, Xin X, Li J, Hou Y, et al. Oligomannurarate sulfate, a novel heparanase inhibitor simultaneously targeting basic fibroblast growth factor, combats tumor angiogenesis and metastasis. Cancer Res ; 66 : — Tan WF, Lin LP, Li MH, Zhang YX, Tong YG, Xiao D, et al. Quercetin, a dietary-derived flavonoid, possesses antiangiogenic potential. Eur J Pharmacol ; : — Lee DH, Lee YJ. Quercetin suppresses hypoxia-induced accumulation of hypoxia-inducible factor-1alpha HIF-1alpha through inhibiting protein synthesis. J Cell Biochem ; : — Zhang C, Yang F, Zhang XW, Wang SC, Li MH, Lin LP, et al. Grateloupia longifolia polysaccharide inhibits angiogenesis by downregulating tissue factor expression in HMEC-1 endothelial cells. Bello E, Colella G, Scarlato V, Oliva P, Berndt A, Valbusa G, et al. E is a potent dual inhibitor of VEGFR and FGFR that exerts antitumor activity in multiple preclinical models. Cancer Res ; 71 : — Chiu P, Leung LT, Ko BC. Pseudolaric acids: isolation, bioactivity and synthetic studies. Nat Prod Rep ; 27 : — Yang SP, Cai YJ, Zhang BL, Tong LJ, Xie H, Wu Y, et al. Structural modification of an angiogenesis inhibitor discovered from traditional Chinese medicine and a structure-activity relationship study. J Med Chem ; 51 : 77— Miao ZH, Ding J. Transcription factor c-Jun activation represses mdr-1 gene expression. Cancer Res ; 63 : — CAS PubMed Google Scholar. Miao ZH, Tang T, Zhang YX, Zhang JS, Ding J. Cytotoxicity, apoptosis induction and downregulation of MDR-1 expression by the anti-topoisomerase II agent, salvicine, in multidrug-resistant tumor cells. Weidemann A, Johnson RS. Biology of HIF-1alpha. Cell Death Differ ; 15 : —7. Semenza GL. Hydroxylation of HIF oxygen sensing at the molecular level. Physiology Bethesda ; 19 : — CAS Google Scholar. Epstein AC, Gleadle JM, McNeill LA, Hewitson KS, O'Rourke J, Mole DR, et al. C elegans EGL-9 and mammalian homologs define a family of dioxygenases that regulate HIF by prolyl hydroxylation. Cell ; : 43— Berra E, Ginouves A, Pouyssegur J. The hypoxia-inducible-factor hydroxylases bring fresh air into hypoxia signalling. EMBO Rep ; 7 : 41—5. Rosenzweig SA. Acquired resistance to drugs targeting receptor tyrosine kinases. Biochem Pharmacol ; 83 : —8. Bergers G, Hanahan D. Modes of resistance to anti-angiogenic therapy. Li QN, Liu HY, Xin XL, Pan QM, Wang L, Zhang J, et al. Marine-derived oligosaccharide sulfate JG3 suppresses heparanase-driven cell adhesion events in heparanase over-expressing CHO-K1 cells. Acta Pharmacol Sin ; 30 : —8. Download references. The authors sincerely thank all of the individuals who have contributed to the work that has been reviewed in this article, including all of the faculty members, postdoctors and students who were either directly or indirectly involved in antiangiogenic studies in the Division of Antitumor Pharmacology, as well as all of our collaborators in the Natural Products Chemistry and Medicinal Chemistry fields who provided us with the compounds that were used in the studies that have been reviewed in this paper. Division of Antitumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, , China. You can also search for this author in PubMed Google Scholar. Correspondence to Ze-hong Miao or Jian Ding. Reprints and permissions. Miao, Zh. Newly discovered angiogenesis inhibitors and their mechanisms of action. Acta Pharmacol Sin 33 , — Download citation. Received : 15 June Accepted : 19 June Published : 27 August Issue Date : September 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. Skip to main content Thank you for visiting nature. nature acta pharmacologica sinica review article. Download PDF. Abstract In the past decade, the success of angiogenesis inhibitors in clinical contexts has established the antiangiogenic strategy as an important part of cancer therapy. Angiogenic signaling pathways and anti-angiogenic therapy for cancer Article Open access 11 May Design, synthesis and evaluation of novel tetrahydropyridothienopyrimidin-ureas as cytotoxic and anti-angiogenic agents Article Open access 11 June Andrographolide binds to ATP-binding pocket of VEGFR2 to impede VEGFA-mediated tumor-angiogenesis Article Open access 11 March Introduction Angiogenesis drives tumor progression; in particular, angiogenesis is critical for the growth and metastasis of solid tumors 1 , 2 , 3 , 4. Table 1 Angiogenesis inhibitors discovered in the Shanghai Institute of Materia Medica since Full size table. An overview of the 17 antiangiogenic compounds In a search for new angiogenesis inhibitors, we performed extensive evaluations of thousands of natural products and synthetic or semi-synthetic compounds over the course of the past 10 years. Figure 1. Full size image. The discovery that the stability of HIF-1α protein is regulated by c-Jun based on mechanistic studies of the antiangiogenic activity of pseudolaric acid B Pseudolaric acid B is a diterpenoid isolated from the root bark of Pseudolarix amabilis Figure 2. The development of AL as a clinically promising angiokinase inhibitor Various PTKs are aberrantly activated during tumor progression. Concluding remarks As an aspect of international efforts to explore new antiangiogenic compounds, we investigated the inhibition of angiogenesis by 17 compounds. Similar content being viewed by others. References Zetter BR. Article CAS Google Scholar Eichhorn ME, Kleespies A, Angele MK, Jauch KW, Bruns CJ. Article CAS Google Scholar Fischer C, Mazzone M, Jonckx B, Carmeliet P. Article CAS Google Scholar Argyriou AA, Giannopoulou E, Kalofonos HP. Article CAS Google Scholar Tugues S, Koch S, Gualandi L, Li X, Claesson-Welsh L. Article CAS Google Scholar Chen Y, Zhang YX, Li MH, Zhao WM, Shi YH, Miao ZH, et al. Article CAS Google Scholar Tong Y, Zhang X, Zhao W, Zhang Y, Lang J, Shi Y, et al. Article CAS Google Scholar Ma J, Xin X, Meng L, Tong L, Lin L, Geng M, et al. Article Google Scholar Tian F, Zhu CH, Zhang XW, Xie X, Xin XL, Yi YH, et al. Article CAS Google Scholar Tong Y, Zhang X, Tian F, Yi Y, Xu Q, Li L, et al. Article CAS Google Scholar Zhou Y, Chen Y, Tong L, Xie H, Wen W, Zhang J, et al. Article CAS Google Scholar Sun QM, Miao ZH, Lin LP, Gui M, Zhu CH, Xie H, et al. Article CAS Google Scholar Guo XN, Zhong L, Tan JZ, Li J, Luo XM, Jiang HL, et al. Article CAS Google Scholar Zhong L, Guo XN, Zhang XH, Sun QM, Tong LJ, Wu ZX, et al. Article CAS Google Scholar Yu B, Miao ZH, Jiang Y, Li MH, Yang N, Li T, et al. Article CAS Google Scholar Yu B, Li MH, Wang W, Wang YQ, Jiang Y, Yang SP, et al. Article CAS Google Scholar Dai M, Miao ZH, Ren X, Tong LJ, Yang N, Li T, et al. Article CAS Google Scholar Li MH, Miao ZH, Tan WF, Yue JM, Zhang C, Lin LP, et al. Article CAS Google Scholar Xiao D, Tan W, Li M, Ding J. Article CAS Google Scholar Zhou ZL, Luo ZG, Yu B, Jiang Y, Chen Y, Feng JM, et al. Google Scholar Zhou ZL, Yang YX, Ding J, Li YC, Miao ZH. Article CAS Google Scholar Wong VK, Chiu P, Chung SS, Chow LM, Zhao YZ, Yang BB, et al. Tumors can also stimulate nearby normal cells to produce angiogenesis signaling molecules. Because tumors cannot grow beyond a certain size or spread without a blood supply, scientists have developed drugs called angiogenesis inhibitors, which block tumor angiogenesis. The goal of these drugs, also called antiangiogenic agents, is to prevent or slow the growth of cancer by starving it of its needed blood supply. Angiogenesis inhibitors are unique cancer-fighting agents because they block the growth of blood vessels that support tumor growth rather than blocking the growth of tumor cells themselves. Angiogenesis inhibitors interfere in several ways with various steps in blood vessel growth. Some are monoclonal antibodies that specifically recognize and bind to VEGF. When VEGF is attached to these drugs, it is unable to activate the VEGF receptor. Some angiogenesis inhibitors are immunomodulatory drugs—agents that stimulate or suppress the immune system —that also have antiangiogenic properties. In some cancers, angiogenesis inhibitors appear to be most effective when combined with additional therapies. Because angiogenesis inhibitors work by slowing or stopping tumor growth without killing cancer cells, they are given over a long period. The U. Food and Drug Administration FDA has approved a number of angiogenesis inhibitors to treat cancer. |
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