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

Although the overproduction of prostaglandin E2 (PGE2) 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 PGE2-mediated cell proliferation and the effect of resveratrol on the proliferation of human colon cancer cells in terms of the modulating PGE2-mediated signaling pathway. PGE2 stimulated the proliferation of several human colon cancer cells and activated growth-stimulatory signal transduction, including Akt and ERK. PGE2 also increased the phosphorylation of GSK-3β, the translocation of β-catenin into the nucleus, and the expressions of c-myc and cyclin D1. Resveratrol, a cancer chemo- preventive phytochemical, however, inhibited PGE2-induced growth stimulation and also suppressed PGE2- mediated signal transduction, as well as β-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.