Green tea catechin, epigallocatechin‐3‐gallate, inhibits vascular endothelial growth factor angiogenic signaling by disrupting the formation of a receptor complex

Abstract

A potential mechanism by which green tea may prevent cancer development is through the inhibition of angiogenesis. We have shown previously that the green tea catechin, epigallocatechin gallate (EGCG), inhibits endothelial cell tube formation through the inhibition of vascular endothelial growth factor (VEGF)-induced Akt activation and vascular endothelial (VE)-cadherin phosphorylation. Furthermore, EGCG can suppress oxidant-induced production of the proangiogenic cytokine interleukin (IL)-8. To further elucidate the antiangiogenic mechanisms of EGCG, we investigated its regulation of other molecular processes in VEGFinduced signaling in human umbilical vein endothelial cells (HUVECs). We show that EGCG at physiological doses (0.5-10 lM) markedly inhibits the formation of a vascular endothelial growth factor receptor 2 complex formed upon the binding of its ligand VEGF. This disruption results in a significant and dosedependent decrease in PI3-kinase activity. Electrophoretic mobility shift assay revealed that EGCG decreased the PI3 kinasedependent activation and DNA-binding ability of NF-jB, likely acting through decreasing phosphorylation and degradation of IjB. VEGF-induced IL-8 production at the mRNA (real time RT-PCR) and protein levels (ELISA) are also suppressed with EGCG. These results suggest a novel mechanism for green tea's anticancer effects where EGCG can abrogate VEGF signaling by interfering with the formation of a receptor complex, resulting in attenuated mitogenic and angiogenic signaling. ' 2005 Wiley-Liss, Inc.

Preparation of arginine–glycine–aspartic acid-modified biopolymeric nanoparticles containing epigalloccatechin-3-gallate for targeting vascular endothelial cells to inhibit corneal neovascularization

“…11,12 EGCG can inhibit angiogenesis by inhibiting the growth of endothelial cells and significantly reducing VEGF-induced corneal NV. 13 Green tea can also inhibit inflammation and angiogenesis.…”

Tea and human health: biomedical functions of tea active components and current issues

“…As for the actual mechanism of any anti-cancer activity of tea, candidates include the antioxidant, induction of phase II enzymes, inhibition of cell proliferation, induction of apoptosis, inhibition of angiogenesis (Fassina et al, 2004;Oak et al, 2005;Rodriguez et al, 2006), direct binding to target molecules, including the inhibition of selected protein kinases, matrix metalloproteinases, and DNA methyltransferases (Lee et al, 2005;Yang et al, 2006;Pham-Huy et al, 2008). The optimal dose of tea components for cancer reduction has yet to be established, thus demanding further scrutiny.…”

Prognostic significance of microvessel density and other variables in Japanese and British patients with primary invasive breast cancer

“…Therefore, we investigated MVD as a possible mechanism, because the Japanese diet is rich in antioxidants and green tea, consumed many times daily by the average Japanese and contains active antiangiogenic substances (Sartippour et al, 2002;Rodriguez et al, 2006). Thus, dietary differences involving these agents was a possible factor.…”