Suppression of Prostaglandin E2-Mediated Cell Proliferation and Signal Transduction by Resveratrol in Human Colon Cancer Cells

Abstract

Although the overproduction of prostaglandin <TEX>$E_2$</TEX> (<TEX>$PGE_2$</TEX>) in intestinal epithelial cells has been considered to be highly correlated with the colorectal carcinogenesis, the precise mechanism of action remains poorly elucidated. Accumulating evidence suggests that the PGE receptor (EP)-mediated signal transduction pathway might play an important role in this process. In the present study, we investigated the mechanism of action underlying <TEX>$PGE_2$</TEX>-mediated cell proliferation and the effect of resveratrol on the proliferation of human colon cancer cells in terms of the modulating <TEX>$PGE_2$</TEX>-mediated signaling pathway. <TEX>$PGE_2$</TEX> stimulated the proliferation of several human colon cancer cells and activated growth-stimulatory signal transduction, including Akt and ERK. <TEX>$PGE_2$</TEX> also increased the phosphorylation of GSK-<TEX>$3{\beta}$</TEX>, the translocation of <TEX>${\beta}$</TEX>-catenin into the nucleus, and the expressions of c-myc and cyclin D1. Resveratrol, a cancer chemopreventive phytochemical, however, inhibited <TEX>$PGE_2$</TEX>-induced growth stimulation and also suppressed <TEX>$PGE_2$</TEX>-mediated signal transduction, as well as <TEX>${\beta}$</TEX>-catenin/T cell factor-mediated transcription in human colon cancer cells. These findings present an additional mechanism through which resveratrol affects the regulation of human colon cancer cell growth.