Inhibition of the vascular-endothelial growth factor-induced intracellular signaling and mitogenesis of human endothelial cells by epigallocatechin-3 gallate

Galloyl group-containing catechins, such as epigallocatechin-3 gallate, inhibit receptor tyrosine kinase activity of several growth factor receptors. This study investigated the effects of epigallocatechin-3 gallate, as compared to epicatechin, on vascular endothelial growth factor-induced intracellular signaling and mitogenesis of human umbilical endothelial cells. Epigallocatechin-3 gallate concentration-dependently inhibited vascular endothelial growth factor-induced DNA synthesis, cell proliferation, autophosphorylation of vascular endothelial growth factor receptors-1 and -2, phosphorylation of extracellular signal-regulated kinases-1 and -2, and mRNA expression of the early growth response factor-1. In contrast, epicatechin was not effective. Thus, epigallocatechin-3 gallate may be an attractive candidate drug to inhibit tumour angiogenesis. (C) 2003 Elsevier B.V. All rights reserved.