Regulation of cell survival by resveratrol involves inhibition of NFκB-regulated gene expression in prostate cancer cells

Abstract

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 NFκB activity in LNCaP cells (inducible NFκB), and PC-3 cells (constitutive NFκB) are reported. METHODS. Cells were treated with 1-150 μM of RES during 36 hr. NFκB subcellular localization was analyzed by western blot and immunofluorescence. IκBα was evaluated by immunoprecipitation followed by Western blot. Specific DNA binding of NFκB was determined by EMSA assays and NFκB-mediated transcriptional activity by transient transfection with a luciferase gene reporter system. RESULTS. RES induced a dose-dependent cytoplasmic retention of NFκB mediated by IκBα in PC-3 cells but not in LNCaP. RES-induced inhibition ofNFκB specific binding toDNAwas more significant in PC-3 cells. NFκB-mediated transcriptional activity induced by EGF and TNFα were inhibited by RES i