Green tea catechins inhibit vascular endothelial growth factor receptor phosphorylation.
Vascular endothelial growth factor (VEGF) receptors (VEGFR) play a major role in tumor angiogenesis and, thus, represent attractive targets for the development of novel anticancer therapeutics. In this work, we report that green tea catechins are novel inhibitors of VEGFR-2 activity. Physiological concentrations (0.01-1 microM) of epigallocatechin-3 gallate, catechin-3 gallate, and, to a lesser extent, epicatechin-3 gallate induce a rapid and potent inhibition of VEGF-dependent tyrosine phosphorylation of VEGFR-2. The inhibition of VEGFR-2 by epigallocatechin-3 gallate was similar to that induced by Semaxanib (SU5416), a specific VEGFR-2 inhibitor. The inhibition of VEGFR-2 activity by the catechins displayed positive correlation with the suppression of in vitro angiogenesis. These observations suggest that the anticancer properties of green tea extracts may be related to their inhibition of VEGF-dependent angiogenesis.
Lamy
Sylvie
S
Laboratoire de Médecine Moléculaire, Centre de Cancérologie Charles-Bruneau, Hôpital Ste-Justine et Université du Québec à Montréal, Montréal, Québec H3C 3P8, Canada.
Gingras
Denis
D
Béliveau
Richard
R
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D001628:Beverages; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002417:Cattle; D002478:Cells, Cultured; D002642:Chick Embryo; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D007700:Kinetics; D018919:Neovascularization, Physiologic / Q000187:drug effects; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D017978:Receptors, Growth Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D040262:Receptors, Vascular Endothelial Growth Factor
D020533:Angiogenesis Inhibitors; D017978:Receptors, Growth Factor; C417939:catechin gallate; D002392:Catechin; C062669:epicatechin gallate; C045651:epigallocatechin gallate; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor