Regulation of Cell Survival by Resveratrol Involves Inhibition of NFκB-Regulated Gene Expression in Prostate Cancer Cells

BACKGROUND. Polyphenols have been proposed as antitumoral agents. We have shown that resveratrol (RES) induced cell cycle arrest and promoted apoptosis in prostate cancer cells by inhibition of the PI3K pathway. The RES effects on NF kappa B activity in LNCaP cells (inducible NF kappa B), and PC-3 cells (constitutive NF kappa B) are reported. METHODS. Cells were treated with 1-150 mu M of RES during 36 hr. NF kappa B subcellular localization was analyzed by western blot and immunofluorescence. I kappa B alpha. was evaluated by immunoprecipitation followed by Western blot. Specific DNA binding of NF kappa B was determined by EMSA assays and NF kappa B-mediated transcriptional activity by transient transfection with a luciferase gene reporter system. RESULTS. RES induced a dose-dependent cytoplasmic retention of NF kappa B mediated by I kappa B alpha in PC-3 cells but not in LNCaP. RES-induced inhibition of NF kappa B specific binding to DNA was more significant in PC-3 cells. NF kappa B-mediated transcriptional activity induced by EGF and TNF alpha were inhibited by RES in both cell lines. LY294002 mimicked RES effects on NF kappa B activity. CONCLUSION. Antiproliferative and apoptotic effects of RES on human prostate cancer cells may be mediated by the inhibition of NF kappa B activity. This mechanism seems to be associated to RES-induced PI3K inhibition. RES could have therapeutic potential for prostate cancer treatment. Prostate 69: 1.045-1054, 2009. (C) 2009 Wiley-Liss, Inc.