The
polyphenol epigallocatechin-3-gallate (EGCG), the principal mediator of the
green tea, has been known to possess antitumor effect. The
endothelin A receptor (ET(A)R)/
endothelin-1 (ET-1) axis is overexpressed in ovarian
carcinoma representing a novel therapeutic target. In this study, we examined the
green tea and EGCG effects on two ovarian
carcinoma cell lines, HEY and OVCA 433. EGCG inhibited
ovarian cancer cell growth and induced apoptosis that was associated with a decrease in Bcl-X(L) expression and activation of
caspase-3. Treatment with
green tea or EGCG inhibited ET(A)R and ET-1 expression and reduced the basal and ET-1-induced cell proliferation and invasion. The EGCG-induced inhibitory effects were associated with a decrease of ET(A)R-dependent activation of the p42/p44 and
p38 mitogen-activated protein kinases and
phosphatidylinositol 3-kinase pathway. Remarkably, EGCG treatment resulted in a lowering of basal and ET-1-induced angiogenesis and invasiveness mediators, such as
vascular endothelial growth factor and
tumor proteinase activation. Finally, in HEY ovarian
carcinoma xenografts,
tumor growth was significantly inhibited by
oral administration of
green tea. This effect was associated with a reduction in ET-1, ET(A)R, and
vascular endothelial growth factor expression, microvessel density, and proliferation index. These results provide a novel insight into the mechanism by which EGCG, affecting multiple ET(A)R-dependent pathways, may inhibit ovarian
carcinoma growth, suggesting that EGCG may be useful in preventing and treating ovarian
carcinoma in which ET(A)R activation by ET-1 plays a critical role in
tumor growth and progression.