Resveratrol interferes with AKT activity and triggers apoptosis in human uterine cancer cells

High-dose of resveratrol triggered apoptosis in five out of six uterine cancer cell lines, as judged from Hoechst nuclear staining and effector caspase cleavage. In accordance, uterine cancer cell proliferation was decreased. Resveratrol also reduced cellular levels of the phosphorylated/active form of anti-apoptotic kinase AKT. Endogenous COX-2 protein levels were decreased, concomitant with a decrease in production of COX metabolites PGE2 and PGF2α, in each uterine cancer cell line expressing detectable levels of COX-1 and/or COX-2 in presence of resveratrol. Although COX expression was identified as a target of resveratrol in uterine cancer cells, inhibition of COX activity or exogenously added PGE2 did not modulate the effect of resveratrol on cellular proliferation.High-dose of resveratrol exerts tumoricidal activity over uterine cancer cells and regulates COX expression. In these cells, resveratrol would not directly target COX activity, but possibly other enzymes involved in prostaglandin synthesis that act downstream of the COXs.Resveratrol (3,4',5-trihydroxy-trans-stilbène) is a natural phytoalexin present in grape skins and consequently, in red wines and grape juices [1,2]. When used at low concentrations resveratrol has cytoprotective activity, which is mostly attributed to its antioxidant properties [3]. However, when administered at higher doses, resveratrol possesses anti-cancer activity by interfering with different cellular events associated with initiation, promotion and progression of multi-stage carcinogenesis [4]. The chemopreventive activity of resveratrol has notably been demonstrated in breast [5] and prostate [6] cancers. The anticancer potential of resveratrol in endometrial carcinoma, however, remains unknown.Endometrial carcinoma is the fourth type of cancer with respect to incidence rates and is the leading type of gynecological cancer in the Western world. In mutated-PTEN endometrial tumors, which constitute around 50% of all tumors [7],