Antitumor effect of green tea polyphenol epigallocatechin-3-gallate in ovarian carcinoma cells: Evidence for the endothelin-1 as a potential target

The green tea polyphenol, epigallocatechin-3-gallate (EGCG), has been shown to prevent cancer; however, a precise mechanism responsible for tumor growth inhibition has not yet been clearly described. The endothelin (ET) A receptor (ET_AR)/ET-1 autocrine pathway is overexpressed in ovarian carcinoma and triggers tumor growth, neoangiogenesis, and invasion. These latter tumor-promoting effects are mediated through the activation of cyclooxygenase (COX)-1- and COX-2-dependent pathways by ET-1. In the present study, pretreatment of HEY and OVCA 433 ovarian carcinoma cell lines with green tea and EGCG inhibited ET-1/ET_AR expression, ET_AR-mediated COX-1/2 mRNA expression, and COX-2 promoter activity. These effects were associated with a significant reduction in the COX-1/2-derived prostaglandin E₂ (PGE₂) production. These results provide a novel insight into the mechanism by which EGCG, by affecting ET_AR-dependent COX-1/2 pathways may inhibit ovarian tumors suggesting that EGCG may be useful in preventing and treating ovarian carcinoma in which activation of ET _AR by ET-1 plays a critical role in tumor growth and progression.