Angiogenesis Inhibition by Antioxidants
International Journal of Biomedical Science and Engineering
Volume 2, Issue 6-1, December 2014, Pages: 7-19
Received: Oct. 9, 2014; Accepted: Dec. 12, 2014; Published: Dec. 30, 2014
Views 3389      Downloads 154
Carlos André Prauchner, Departamento de Química, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, CEP 97105-900, Santa Maria, RS, Brasil
Article Tools
Follow on us
Reducing cancer morbidity and mortality requires several synergic approaches target on tumoural cells and their environment. Angiogenesis is the development of new blood vessels from the pre-existing vasculature. This process is normally observed only transiently during embryogenesis, and in adulthood, during wound healing and uterus function. However, pathologic angiogenesis is involved in some diseases, including cancer. Tumoural angiogenesis favors cancer invasion and metastasis emission. Normally, endothelial cells are maintained in a latent state, but under determined stimulus they suffer activation, a process called “angiogenic switch”. Among stimulatory angiogenic factors are vascular endothelial growth factor (VEGF), angiopoetin-1 and 2, interleukin-8 (IL-8), fibroblast growth factor basic (bFGF), platelet-derived growth factor (PDGF) and angiotensin II. Furthermore, matrix metalloproteinases (MMPs), especially MMP-2 and MMP-9, play role in angiogenesis. Reactive oxygen species (ROS), as hydrogen peroxide (H2O2), participates in angiogenesis signaling through VEGF receptors, mainly VEGFR2 (Flk-1/KDR), and angiopoietin-I/Tie-2 receptors. The major source of ROS in endothelial cells is the enzyme NAD(P)H oxidase, but the role of nitric oxide (NO•), from endothelial nitric oxide synthase (eNOS), should not be neglected. Moreover, oxidized phospholipids and products from arachidonic acid metabolism can participate in angiogenesis induction. Then, it would be likely that antioxidants could inhibit angiogenesis. Really, a number of studies demonstrated that several antioxidants found in natural products (catechins from teas, resveratrol, polyphenols, flavonoids, isoflavones, lycopene, pigment epithelium-derived factor, glutathione); nutritional components (vitamins C, D, E, β-carotene and selenium); and semi-synthetic and synthetic compounds (N-acetylcysteine, L-NAME, L-NIO, sodium piruvate, pyrrolidine dithiocarbamate, and organoselenium compounds) were able to inhibit angiogenesis. These compounds were tested in several in vitro assays and in vivo animal models and inhibited angiogenesis via redox-sensitive and insensitive mechanisms. Thus, the consumption of antioxidants from natural sources can be recommended in face to benefic effects related to angiogenesis inhibition, while high fat diet can be undesired. In addition, some semi-synthetic and synthetic compounds has potential as future drugs for inhibiting tumoural angiogenesis, but it needs more detailed studies in terms of efficacy and security.
Cancer, Angiogenesis, Reactive Oxygen Species, Antioxidants, Selenium
To cite this article
Carlos André Prauchner, Angiogenesis Inhibition by Antioxidants, International Journal of Biomedical Science and Engineering. Special Issue:Cancer Research. Vol. 2, No. 6-1, 2014, pp. 7-19. doi: 10.11648/j.ijbse.s.2014020601.12
Abe R, Shimizu T, Yamagishi S-I, Shibaki A, et al.(2004). Overexpression of pigment epithelium-derived factor decreases angiogenesis and inhibits the growth of human malignant melanoma cells in vivo. Am. J. Pathol. 164(4):1225-1232.
Annabi B, Lachambre MP, Bousquet-Gagnon N, Page M, Gingras D, Beliveau R.(2002). Green tea polyphenol (-)epigallocatechin 3-gallate inhibits MMP-2 secretion and Mt1-MMP-driven migration in glioblastome cells. Biochim. Biophys. Acta 1542:209-220.
Arbiser JL, Klauber N, Rohan R, Van Leeuwen R, Huang MT, Fisher C, et al.(1998). Curcumin is an in vivo inhibitor of angiogenesis. Mol. Med. 4:376–383.
Arbiser JL, Petros J, Klafter R, Govindajaran B, McLaughlin ER, Brown LF, Cohen C, Moses M, Kilroy S, Arnold RS, Lambeth JD.(2002). Reactive oxygen generated by Nox1 triggers the angiogenic switch. Proc. Natl. Acad. Sci. USA 99(2):715-720.
Armstrong AW, Voyles SV, Armstrong EJ, Fuller EN, Rutledge JC.(2011). Angiogenesis and oxidative stress: Common mechanisms linking psoriasis with atherhosclerosis. J. Dermatol. Sci. 63:1-9.
Barbosa NBV, Nogueira, CW, Guecheva TN, Bellinaso ML, Rocha JBT.(2008). Diphenyl diselenide supplementation delays the development of N-nitroso-N-methylurea-induced mammary tumours. Arch. Toxicol. 82:655-663.
Bell L, Madri JA.(1990). Influence of angiotensin system on endothelial and smooth muscle cell migration. Am. J. Pathol. 137:7-12.
Bochkov VN, Philippova M, Oskolkova O, Kadl A, Furnkranz A, et al.(2006). Oxidized phospholipids stimulate angiogenesis via autocrine mechanisms, implicating a novel role for lipid oxidation in the evolution of atherosclerotic lesions. Circ. Res. 99:900-908.
Borges LP, Nogueira CW, Panatieri RB, Rocha JBT, Zeni GR.(2006). Acute liver damage induced by 2-nitropropane in rats: Effect of diphenyl diselenide on antioxidant defenses. Chem. Biol. Interact. 160:90-107.
Brakenhielm E, Cao R, Cao Y.(2001). Supression of angiogenesis, tumour growth, and wound healing by resveratrol, a natural compound in red wine and grapes. FASEB J. 15:1798-1800.
Brucker W, Rohde HG.(1968). Effect of selenium organic compounds on the radiation effect of Phycomyces blakesleanus. Pharmazie 23:310-315.
Büchler P, Reber HA, Büchler MW, Friess H, Lavey RS, Hines OJ.(2004). Antiangiogenic activity of genistein in pancreatic carcinoma cells is mediated by the inhibition of hypoxia-inducible factor-1 and the down-regulation of VEGF gene expression. Cancer 100:201–210.
Cai, H.(2005). Hydrogen peroxide regulation of endothelial function: Origins, mechanisms, and consequences. Cardiovasc. Res. 68:26-36.
Cao Y, Cao R.(1999). Angiogenesis inhibited by drinking tea. Nature 398:381.
Carmeliet P.(2000). Mechanisms of angiogenesis and arteriogenesis. Nat. Med. 6:389-395.
Carmeliet P.(2005). Angiogenesis in life, disease and medicine. Nature 438:932-936.
Chua CC, Hamdy RC, Chua BHL.(1998). Upregulation of vascular endothelial growth factor by H2O2 in rat heart endothelial cells. Free Radical Biol. Med. 25(8):891-897.
Chen ML, Lin YH, Hu ML.(2012). Lycopene inhibits angiogenesis both in vitro and in vivo by inhibiting MMP-2/uPA system through VEGFR2-mediated PI3k-Akt and ERK/p38 signaling pathways. Mol. Nutr. Food Res. 56(6):889-899.
Chen A., Xu J, Johnson AC.(2006). Curcumin inhibits human colon cancer cell growth by suppressing gene expression of epidermal growth factor receptor through reducing the activity of the transcription factor Egr-1. Oncogene 25:278–287.
Cherrington JM, Strawn LM, Shawver LK.(2000). New paradigms for the treatment of cancer: The role of anti-angiogenesis agents. Adv. Cancer Res. 79:1-38.
Colavitti R, Pani G, Bedogni B, Azevino R, Borrello S, Waltenberger J, Galeotti T.(2002). Reactive oxygen species as dowstream mediators of angiogenic signaling by vascular endothelial growth factor receptor-2KDR. J. Biol. Chem. 277(2):3101-3108.
Coultas L, Chawengsaksophak K, Rossant J.(2005). Endothelial cells and VEGF in vascular development. Nature 438:937-945.
Coussens LM, Werb Z.(2002). Inflammation and cancer. Nature 420:860-867.
Crawford HC, Matrisian LM.(1996). Mechanisms controlling the transcription of matrix metalloproteinase genes in normal and neoplastic cells. Enzyme Protein 49: 20-37.
De Flora S, Ferguson LR.(2005). Overview of mechanisms of cancer chemopreventive agents. Mutat. Res. 591:8-15.
Doná M, Dell’Aica I, Calabrese F, Benelli R, Morini M, Albini A, Garbisa S.(2003). Neutrophil restraint by green tea: inhibition of inflammation, associated angiogenesis, and pulmonary fibrosis. J. Immunol. 170:4335-4341.
Dong Z, Ma W-Y, Huang C, Yang CS.(1997). Inhibition of tumour promoter-induced activator protein 1 activation and cell transformation by tea polyphenols, (-)-epigallocatechin gallate, and theaflavins. Cancer Res. 57:4414-4419.
El Bedoui J, Oak MH, Anglard P, Schini-Kerth VB.(2004). Green tea extract strongly prevents thrombin-induced pro-MMP-2 expression and its conversion to MMP-2 by directly inhibiting MT1-MMP in vascular smooth muscle cells. Fundam. Clin. Pharmacol. 18:243.
Elgass S, Cooper A, Chopra M.(2012). Lycopene inhibits angiogenesis in human umbilical vein endothelial cells and rat aortic rings. Br. J. Nutr. 108(3):431-439.
Emanueli C, Salis MB, Stacca T, Pinna A, Gaspa L, Madeddu P.(2002). Angiotensin AT(1) receptor signaling modulates reparative angiogenesis induced by limb ischemia. Br. J. Pharmacol. 135:87-92.
Flamme I, Risau W.(1992). Induction of vasculogenesis and hematopoiesis in vitro. Development 116:435-439.
Folkman J.(1971). Tumour angiogenesis: therapeutic implications. New Engl. J. Med. 285:1182-1186.
Folkman J.(1990). What is evidence that tumours are angiogenesis dependent? J. Natl. Cancer. Inst. 82:4-6.
Folkman J.(1995). Angiogenesis in cancer, vascular, rheumathoid and other disease. Nat. Med. 1:27-31.
Folkman J, Klagsbrum M.(1987). Angiogenic factors. Science 235:442-447.
Folkman J, Handfelt P, Hlatky, L.(2000). Cancer: looking outside of genoma. Nat. Rev. Mol. Cell Biol. 1:76-79.
Fotsis T, Pepper M, Adlercreutz H, Fleischmann G, Hase T, Montesano R, Schweigerer L.(1993). Genistein, a dietary-derived inhibitor of in vitro angiogenesis. Proc. Natl. Acad. Sci. USA 90:2690–2694.
Fotsis T, Pepper M, Adlercreutz H, Hase T, Montesano R, Schweigerer L.(1995). Genistein, a dietary ingested isoflavonoid, inhibits cell proliferation and in vitro angiogenesis. J. Nutr. 125(suppl. 3):790S–797S.
Frankel EN, Kanner J, German JB, Parks E, Kinsella JE.(1993). Inhibition of oxidation of human low-density liprotein by phenolic substances in red wine. Lancet 341:454-457.
Gallo, O, Masini E, Morbidelli L, Franchi A, Fini-Storchi I, Vergari WA, Ziche M.(1998). Role of nitric oxide in angiogenesis on tumour progression in head and neck cancer. J. Natl. Cancer Inst. 90:587-596.
Garbisa S, Sartor L, Biggin A, Salvato B, Benelli R, Albini A. Tumour gelatinases and invasion inhibited by tea green tea flavanol epigallocatechin-3-gallate. Cancer 91:822-832.
Gatenby RA, Gillies RJ.(2004). Why do cancer have high aerobic glycolysis? Nat. Rev. Cancer 4:891-899.
Ghosh J.(2004). Rapid induction of apoptosis in prostate cancer cells by selenium: reversal by metabolites of arachidonate 5-lipoxygenase. Biochem. Bioph. Res. Co. 315:624-635.
Goyal P, Weismann N, Grimminger F, Hegel C, Bader L, Rose F, Fink L, Ghofrani HA, Schermuly RT, Schmdit HHH, Seeger W, Hänze J.(2004). Upregulation fo NAD(P)H oxidase I in Hypoxia activates hypoxia-inducible factor 1 via increase in reactive oxygen species. Free Radical Bio. Med. 36(10):1279-1288.
Gururaj AE, Belakavadi M, Venkatesh DA, Marme D, Salimath BP.(2002). Molecular mechanisms of anti-angiogenic effect of curcumin. Biochem. Biophys. Res. Commun. 297: 934–942.
Hahm ER, Gho YS, Park S, Park C, Kim KW, Yang CH.(2004). Synthetic curcumin analogs inhibit activator protein-1 transcription and tumour-induced angiogenesis. Biochem. Bioph. Res. Co. 321(2):337–344.
Hanahan D, Folkman J.(1996). Patterns and emerging mechanism of the angiogenic switch during tumourogenesis. Cell 86:353-354.
Hanasaki Y, Ogawa S, Fukui S.(1994). The correlation between active oxygens scavenging and antioxidative effects of flavonoids. Free Radic. Biol. Med. 16:845-850.
Harfouche R, Malak NA, Brandes RP, Karsan A, Irani K, Hussai SN.(2005). Roles of reactive oxygen species in angiopoietin-1/Tie-2 receptor signaling. FASEB 19:1728-1730.
Ho QT, Kuo CJ.(2007). Vascular endothelial growth factor: Biology and therapeutic applications. Int. J. Biochem. Cell B. 39:1349-1357.
Hood JD, Meininger CJ, Ziche M, Granger HJ.(1998). VEGF upregulates ecNOS message, protein, and NO production in human endothelial cells. Heart Circ. Physiol. 43:H1054-H1058.
Hort MA, Straliotto MR, Netto PM, da Rocha JBT, de Bem AF, Ribeiro-do-Valle RM.(2011). Diphenyl diselenide effectively reduces atherosclerotic lesions in LDLr -/- mice by attenuation of oxidative stress and inflammation. J. Cardiovasc. Pharmacol. 58:91-101.
Huang MT, Lou YR, Ma W, Newmark HL, Reuhl KR, Conney, A.H.(1994). Inhibitory effects of dietary curcumin on forestomach, duodenal, and colon carcinogenesis in mice. Cancer Res. 54:5841–5847.
Ikeda S, Ushio-Fukai M, Zuo L, Tojo T, Alexander RW.(2005). Novel role of ARF6 in vascular endothelial growth factor signaling and angiogenesis. Cir. Res. 96:467-475.
Jankun J, Selman SH, Swiercz R, Akrzypczak-Jankun E. Why drinking green tea could prevent cancer. Nature 387:561.
Jiang C, Jiang W, Ip C, Ganther H, Lu J.(1999). Selenium-induced inhibition of angiogenesis in mammary cancer at chemopreventive levels of intake. Mol. Carcinogen. 26:213-225.
Jiang C, Ganther H, Lu J.(2000). Monomethyl selenium-specific inhition of MMP-2 and VEGF expression: implications for angiogenic switch regulation. Mol. Carcinogen. 29:236-250.
Johnson JJ, Bailey HH, Mukhtar H.(2010). Green tea polyphenols for prostate cancer prevention: A translational perspective. Phytomedicine 17:3-13.
Jung YD, Kim MS, Shin BA, Chay KO, Ahn BW, Liu W, Bucana CD, Gallick GE, Ellis LM.(2001). EGCG, a major component of green tea, inhibits tumour growth by inhibiting VEGF induction in human colon carcinoma cells. Brit. J. Cancer 84(6):844-850.
Khan SG, Katiyar SK, Agarwal R, Mukhtar H.(1992). Enhancement of antioxidant and phase II enzymes by oral feeding of green tea polyphenols in drinking water to SKH-1 hairless mice: possible role in cancer chemoprevention. Cancer Res. 52:4050-4052.
Khatri JJ, Johnson C, Magid R, Lessner SM, Laude KM, Dikalov SI, Harrison DG, Sung H-J, Rong Y, Galis ZS.(2004). Vascular oxidant stress enhances progression and angiogenesis of experimental atheroma. Circulation 109:520-525.
Kim YM, Kim KE, Koh GY, Ho Y-S, Lee K-J.(2006). Hydrogen peroxide produced by angiopoietin-1 mediates angiogenesis. Cancer Res. 66(12):6167-6174.
Kim Y-W, West XZ, Byzova TV.(2013). Inflammation and oxidative stress in angiogenesis and vascular disease. J. Mol. Med. 91:232-328.
Kumamoto M, Nakashima Y, Sueishi K.(1995). Intimal neovascularization in human coronary atherosclerosis its origin and pathophysiological significance. Hum. Pathol. 126:450-456.
Kock AE, Polverini PJ, Kundel SL.(1992). Interleukin-8 a macrophage-derived mediator of angiogenesis. Science 258:1798-1801.
Lakshminarayanan V, Lewallwn M, Frangogiannis NG, Evans AJ, Wedin KE, Michael LH, Entman ML.(2001). Reactive oxygen intermediates induce monocyte chemotactic protein-1 in vascular endothelium after brief ischemia. Am. J. Pathol. 159:1301-1311.
Lee PC, Kibbe MR, Schuchert MJ, Stolz DB, Watkins SC, Griffith BP, Billiar TR, Shears LL.(2000). Nitric oxide induces angiogenesis and upregulates αvβ3 integrin expression on endothelial cells. Microvasc. Res. 60:269-280
Lin JK, Chen PC, Ho CT, Lin-Shiau SY.(2000). Inhibition of xantine oxidase and suppression of intracellular reactive oxygen species in HL-60 cells by theaflavin-3,3’-digallate, (-)-epigallocatechin-3-gallate and propyl gallate. J. Agr. Food Chem. 48:2736-2743.
Lin M-T, Yen M-L, Lin C-Y, Kuo MN.(2003). Inhibition of vascular endothelial growth factor-induced angiogenesis by resveratrol through interruption of Src-dependent vascular endothelial cadherin tyrosine phosphorilation. Mol. Pharmacol. 64(5):1029-1036.
Liu Z, Schwimer J, Liu D, Greenway FL, Anthony CT, Woltering EA.(2005). Black raspberry extract and fractions contain angiogenic inhibitors. J. Agr. Food Chem. 53:3909-3915.
Longo R, Sarmiento R, Fanelli M, Capaccetti B, Gattuso D, Gasparini G.(2002). Anti-angiogenic therapy: Rationale, challenges and clinical studies. Angiogenesis 5:237-256.
López-Lázaro M.(2007). Dual role of peroxide in cancer: Possible relevance to cancer chemoprevention and therapy. Cancer Lett. 252:1-8.
Maeda-Yamamoto M, Kawahara H, Tahara N, Tsuji K, Hara Y, Isemura M.(1999). Effects of tea polyphenols on the invasion on the matrix metalloproteinases acitivities of human fibrosarcoma HT1080 cells. J. Agric. Food Chem. 47:2350-2354.
Malafa MP, Fokum FD, Smith L, Louis A.(2002). Inhibition of angiogenesis and promotion of melanoma dormancy by vitamin E succinate. Ann. Sur. Oncol. 9(10):1023-1032.
Mantell DJ, Owens PE, Bundred NJ, Mawer EB, Canfireld AE.(2000). 1α,25-Dihydroxyvitamin D3 inhibits angiogenesis in vitro and in vivo. Circ. Res. 87:214-220.
Masuda M, Suzui M, Lim JT, Deguchi A, Soh JW, Weinstein IB.(2002). Epigallocatechin 3-gallate decreases VEGF production in head and neck and breast carcinoma cells by inhibiting EGFR-related pathways of signal transduction. J. Exp. Ther. Oncol. 2:350-359.
Maulik N, Das DK.(2002). Redox signaling in vascular angiogenesis. Free Radical Biol. Med. 33(8):1047-1060.
Mautner HG, Kumler WD, Okano Y. Pratt R.(1956). Antifungal activity of some substituted selenosemicarbazones and related compounds. Antibiot. Khemoterap.6:51-55.
McCarty MF.(1998). Polyphenol-mediated inhibition of AP-1 transactivation activity may slow cancer growth by impeding angiogenesis and tumour invasiness. Med. Hypotheses 50:511-514.
Miyagi Y, Miwa K, Inoue H.(1997). Inhibition of human low-density lipoprotein oxidation by flavonoids in red wine and grape juice. Am. J. Cardiol. 80:1627-1631.
Monte M, Davel LE, Lustig S.(1997). Hydrogen peroxide is involved in lymphocyte activation mechanisms to induce angiogenesis. Eur. J. Cancer 33(4):676-682.
Mousa SA, O’Connor L, Rossman TG, Block E.(2007). Pro-angiogenesis action of arsenic and its reversal by selenium-derived compounds. Carcinogenesis 28(5):962-967.
Murohara T, Asahara T.(2002). Nitric oxide and angiogenesis in cardiovascular disease. Antioxid. Redox Signal. 4:825-831.
Nespereira B, Pérez-Ilzarbe M, Fernández P, Fuentes AM, Páramo JÁ, Rodríguez JÁ.(2003). Vitamins C and E downregulate vascular VEGF and VEGFR-2 expression in apoliproteina-E-deficient mice. Atherosclerosis 171:67-73.
Nogueira CW, Zeni GR, Rocha JBT.(2004). Organoselenium and organotellurium compounds: Toxicology and Pharmacology. Chem. Rev. 104:6255-6285.
Nogueira CW, Rocha JBT.(2010). Diphenyl diselenide a janus-faced molecule. J. Braz. Chem. Soc. 21:2055-2071.
Nogueira CW, Rocha JBT.(2011). Toxicology and pharmacology of selenium: emphasis on synthetic organoselenium compounds. Arch. Toxicol. 85:1313-1359.
Oak MH, Chataigneau M, Keravis T, et al.(2003). Red wine polyphenolic compounds inhibit vascular endothelial growth factor expression in vascular smooth muscle cells by preventing the activation of the p38 mitogen-activated protein kinase pathway. Arterioscler. Thromb. Vasc. Biol. 23:1001-1007.
Oak MH, El Bedoiu J, Anglard P, Schini-Kerth VB.(2004). Red wine polyphenolic compounds strongly inhibit pro-MMP2 activation in response to thrombin via direct inhibition of MT1-MMP in vascular smooth cells. Circulation 110(13):1861-1867.
Oikawa T, Hirotani K, Ogasawara H, et al.(1990). Inhibition of angiogenesis by vitamin D3 analgues. Eur. J. Pharmacol. 178:247-250.
Oliner J, Min, H, Leal J, Yu D, Rao S, You E, et al.(2004). Supression of angiogenesis and tumour growth by selective inhibition of angiopoietin-2. Cancer Cell 6:507-516.
Otani A, Takagi H, Suzuma K, Honda Y.(1998). Angiotensin II potentiates vascular endothelial growth factor-induced angiogenic activity in retinal microcapillary endothelial cells. Circ. Res. 82:619-628.
Pepper MS.(2001). Role of matrix metalloproteinase and plasminogen activator-plasmin systems in angiogenesis. Arterioscler. Thromb. Vasc. Biol. 21:1104-1117.
Polytarchou C, Papadimitriou E.(2005). Antioxidants inhibit human endothelial cell functions through down-regulation of endothelial nitric oxide synthase activity. Eur. J. Pharmacol. 510:31-38.
Posser T, Moretto MB, Dafre AL, Farina M, Rocha JBT, Nogueira CW et al. (2006). Antioxidant effect of diphenyl diselenide against sodium nitriprusside (SNP) induced lipid peroxidation in human platelets and erythrocyte membranes: An in vitro evaluation. Chem. Biol. Interact. 164:126-135.
Posser T, Paula MT, Franco JL, Leal RB, Rocha JBT.(2011). Diphenyl diselenide induces apoptotic cell death and modulates ERK1/2 phosphorilation in human neuroblastoma SH-SY5Ycells. Arch. Toxicol. 85:645-651
Potapova O, Fakharai H, Baird S, et al.(1996). Platelet-derived growth factor-B/v-sis confers a tumourogenic and metastatic phenotype to human T98G glioblastoma cells. Cancer Res. 56:280-286.
Prauchner CA. A importância do selênio para a agropecuária e saúde humana. Santa Maria: EditoraUFSM, 2014. 376 p.
Prauchner CA. Estudo do potencial teratogênico de organocalcogênios e da atividade anti-sepsis e anti-angiogênese do disseleneto de difenila em modelos in vivo. Santa Maria: UFSM (Thesis), 2009. 157 p.
Prauchner CA, Prestes AS, Nogueira CW, Rocha JBT.(2013). Effects of diphenyl diselenide and diphenyl ditellurite on chicken embryo development. Toxicol. Mech. Method. 23:660-664.
Prauchner CA, Prestes AS, Rocha JBT.(2011). Effects of diphenyl diselenide on oxidative strees induced by sepsis in rats. Pathol. Res. Pract. 207:554-558.
Rao CV, Rivenson A, Simi B, Reddy BS.(1995). Chemoprevention of colon carcinogenesis by dietary curcumin, a naturally occurring plant phenolic compound. Cancer Res. 55:259–266.
Rosa RM, Moura DJ, Romano e Silva AC, Henriques JAP.(2007). Antioxidant activity of diphenyl diselenide prevents the genotoxicity of several mutagens in Chinese hamster V79 cells. Mutat. Res. 631:44-54
Rossato JL, Ketzer LA, Centurião FB, Silva SJ, Lüdtke DS, Zeni G, et al. (2000). Antioxidant properties of new chalcogenides against lipid peroxidation in rat brain. Neurochem. Res. 27:297-303.
Roskoski JrR.(2007). Vascular endothelial growth factor (VEGF) signaling in tumour progression. Crit. Rev. Oncol. Hemat. 62:179-213.
Rupil LL, de Bem AF, Roth GA.(2012). Diphenyl diselenide-modulation of macrophage activation: down-regulation of classical and alternative activation markers. Innate Immun. 18:627-637.
Sartippour MR, Shao ZM, Heber D, Beatty P, Zhang L, Liu C, Ellis L, Liu W, Go VL, Brooks MN.(2002). Green tea inhibits vascular endothelial growth factor (VEGF) induction in human breast cancer cells. J. Nutr. 132:2307-2311.
Sasaki K, Murohara T, Ikeda H, Sugaya T, Shimada T, et al.(2002). Evidence for the importance of angiotensin II type 1 receptor in ischemia-induced angiogenesis. J. Clin. Invest. 109:603-611.
Schindler R, Mentlein R.(2006). Flavonoids and vitamin E reduce the release of the angiogenic peptide vascular endothelial growth factor from human tumour cells. J. Nutr. 136:1477-1482.
Schnurr K, Belkner J, Ursini F, Schewe T, Kuhn H.(1996). The selenoenzyme phopholipid hydroperoxide glutathione peroxidase controls the activity of the 15-lipoxygenase with complex substrates and preserves the specificity of the oxygenation products. J. Biol. Chem. 271:4653-4658.
Schwartz JL, Shklar G.(1996). Glutathione inhibits experimental oral carcinogenesis, p53 expression and angiogenesis. Nutr. Cancer 26:229-236.
Sen, CK, Khanna S, Babior BM, Hunt TK, Ellison EC, Roy S.(2002). Oxidant-induced vascular endothelial growth factor expression in human keratinocytes and cutaneous wound healing. J. Biol. Chem. 277(36):33284-33290.
Shen YH, Wang XL, Wilcken DEL.(1998). Nitric oxide induces and inhibits apoptosis through different pathways. FEBS Lett. 433:125-131.
Shim JS, Kim DH, Jung HJ, Kim JH, Lim D, Lee SK, Kim KW, Ahn JW, Yoo JS, Rho JR, Shin J, Kwon HJ.(2002). Hydrazinocurcumin, a novel synthetic curcumin derivative, is a potent inhibitor of endothelial cell proliferation. Bioorganic and Medicinal Chemistry 10 (9):2987–2992.
Shklar G, Schwartz JL.(1996). Vitamin E inhibits experimental carcinogenesis and tumour angiogenesis. Oral Oncology. Eur. J. Cancer 32B:114-119.
Shokravi MT, Marcus DM, Alroy J, Egan K, Saornil MA, Albert DM.(1995). Vitamin D inhibits angiogenesis in transgenic murine retinoblastoma. Invest. Ophth. Vis. Sci. 36(1):83-87.
Shono, T, Ono M, Izumi H, Jimi S-I, Matsushima K, Okamoto T, Kohno K, Kuwano M.(1996). Involvement of the transcription factor NF-κβ in tubular morphogenesis of human microvascular endothelial cells by oxidative stress. Mol. Cell Biol. 16(8):4231-4239.
Schumacher JJ, Upadhyaya P, Ramakrishnan S. (2001). Inhibition of vascular endothelial cells by 1,4-phenylenebis (methylene) selenocyanate – a novel chemopreventive organoselenium compound. Anticancer Res. 21:1945-1951.
Stoclet J-C, Chataigneau T, Ndiaye M, Oak M-O, El Bedoui J, Chataigneau M, Schini-Kerth VB.(2004). Vascular protection by dietary polyphenols. Eur. J. Pharmacol. 500:299-313.
Stoltz, RA, Abrahma NG, Achwartizman ML.(1996). The role of NFκβ in the angiogenic response of coronary microvessel endothelial cells. Proc. Natl. Acad. Sci. USA 93:2832-2837.
Stone JR, Collins T.(2002). The role of hydrogen peroxide in endothelial proliferative responses. Endothelium 9:231-238.
Su CC, Chen GW, Lin JG, Wu LT, Chung JG.(2006). Curcumin inhibits cell migration of human colon cancer colo 205 cells through the inhibition of nuclear factor kappa B/p65 and down-regulates cyclooxygenase-2 and matrix metalloproteinase-2 expressions. Anticancer Res. 26:1281–1288.
Szatrowski TP, Nathan CF.(1991). Production of large amounts of hydrogen peroxide by human tumour cells. Cancer Res. 51:794-798.
Szebenyi G, Fallon JF.(1999). Fibroblast growth factor as multifunctional signaling factors. Int. Rev. Cytol. 185:45-106.
Tang F-Y, Meydani M.(2001). Green tea catechins and vitamin E inhibit angiogenesis of human microvascular endothelial cells through suppression of IL-8 production. Nutr. Cancer 41:119-125.
Thaloor D, Singh AK, Sidhu GS, Prasad PV, Kleinman HK, Maheshwari RK.(1998). Inhibition of angiogenic differentiation of human umbilical vein endothelial cells by curcumin. Cell Growth and Differentiation 9 (4):305–312.
Turk SR, Shipman Jr.C, Drach JC.(1986). Structure-activity relationships among alpha-(N)-heterocyclic acyl thiosemicarbazones and related compounds as inhibitors of herpes simplex virus type 1-specified ribonucleoside diphosphate reductase. J. Gen. Virol. 67:1625-1632.
Tzeng E, Kim Y-M, Pitt BR, Lizonova A, Kovesdi I, Billiar TR.(1997). Adenoviral transfer of the inducible nitric oxide synthase gene blocks endothelial cell apoptosis. Surgery 122:255-263.
Ushio-Fukai M, Alexander RW.(2004). Reactive oxygen species as mediators of angiogenesis signaling (role of NAD(P)H oxidase). Mol. Cell Biochem. 264:85-97.
Ushio-Fukai M.(2006). Redox signaling in angiogenesis: Role of NADPH oxidase. Cardiovas. Res. 71:226-235.
Ushio-Fukai M, Nakamura Y.(2008). Reactive oxygen species and angiogenesis: NADPH oxidase as target for cancer therapy. Cancer Lett. 266:37-52.
Vaupel P.(2004). Tumour microenviroment physiology and its implication radiation oncology. Semin. Radiat. Oncol. 14:198-206.
Weitzel F, Wendel A.(1993). Selenoenzymes regulate the activity of leukocyte 5-lipoxygenase via the peroxide tone. J. Biol. Chem. 268:6288-6292.
West XZ, Malinin NL, Merkulova AA, Tischenko M, Kerr BA, Borden EC, Podrez EA, Salomon RG, Byzova TV.(2006). Oxidative stress induces angiogenesis by activating TLR2 with novel endogenous ligands. Nature 467:972-977.
Yamagishi S-I, Amano S, Inagaki Y, Okamoto T, Takeuchi M, Inoue H.(2003). Pigmenti ephitelium-derived factor inhibits leptin-induced angiogenesis by suppressing vascular endothelial growth factor gene expression through anti-oxidative properties. Microvasc. Res. 65:186-190.
Yamaoka-Tojo M, Ushio-Fukai M, Hilenski L, Dikalov SI, Chen YE, Tojo T, Fukai T, et al.(2004). IQGAP1, a novel vascular endothelial growth factor receptor binding protein, is involved in reactive oxygen species-dependent endothelial migration and proliferation. Cir. Res. 95:276-283.
Yang CS, et al.(1998). Blood and urine levels of tea catechins after ingestion of different amounts of green tea by human volunteers. Cancer epidemiol. Biomark. Prev. 7:351-354.
Yang CS, Wang Z-Y.(1993). Tea and cancer: a review. J. Natl. Cancer Inst. 58:1038-1049.
Yasuda M, Ohzeki Y, Shimizu S, Naito S, Ohtsuru A, Yamamoto T, Kuroiwa Y.(1999). Stimulation of in vitro angiogenesis by hydrogen peroxide and the relation with ETS-1 endothelial cells. Life Sci. 64(4):249-258.
Yoon S-O, Kim M-M, Chung A-S.(2001). Inhibitory effect of selenite on invasion of HT1080 tumour cells. J. Biol. Chem. 276(23):20085-20092.
Zhang G, Miura Y, Yagasaki K.(2000). Supression of adhesion and invasion of hepatoma cell in culture by tea compounds through antioxidative activity. Cancer Lett. 159:169-173.
Zec M, Srdic-Rajic T, Konic-Ristic A, Todorovic T, Andjelkovic K, Filipovic-Ljeskovic I, Radulovic S.(2012). Anti-metastatic and anti-angiogenic properties of potential new anti-cancer drugs based on metal complexes of selenosemicarbazones. Anti-Cancer Agents in Medicinal Chemistry 12:1071-1080.
Ziche M, Morbidelli L, Masini E, Amerini S, Granger HJ, Maggi CA, Geppetti P, Ledda F.(1994). Nitric mediates angiogenesis in vivo and endothelial cell growth and migration in vitro promoted by substance P. J. Clin. Invest. 94:2036-2044.
Zu K, Mucci L, Rosner BA, Clinton SK, Loda M, Stampfer MJ, Giovannucci E.(2014). Dietary lycopene, angiogenesis, and prostate cancer: a prospective study in the prostate-specific antigen era. J. Natl. Cancer Inst. 106(2):430.
Science Publishing Group
1 Rockefeller Plaza,
10th and 11th Floors,
New York, NY 10020
Tel: (001)347-983-5186