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

Benitez, DA; Hermoso, MA; Pozo-Guisado, E; Fernandez-Salguero, PM; Castellon EA.

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 NF?B activity in LNCaP cells (inducible NF?B), and PC-3 cells (constitutive NF?B) are reported. METHODS. Cells were treated with 1-150 µM of RES during 36 hr. NF?B subcellular localization was analyzed by western blot and immunofluorescence. I?Ba was evaluated by immunoprecipitation followed by Western blot. Specific DNA binding of NF?B was determined by EMSA assays and NF?B-mediated transcriptional activity by transient transfection with a luciferase gene reporter system. RESULTS. RES induced a dose-dependent cytoplasmic retention of NF?B mediated by I?Ba in PC-3 cells but not in LNCaP. RES-induced inhibition ofNF?B specific binding toDNAwas more significant in PC-3 cells. NF?B-mediated transcriptional activity induced by EGF and TNFa were inhibited by RES in both cell lines. LY294002 mimicked RES effects on NF?B activity. CONCLUSION. Antiproliferative and apoptotic effects of RES on human prostate cancer cells may be mediated by the inhibition of NF?B activity. This mechanism seems to be associated to RES-induced PI3K inhibition. RES could have therapeutic potential for prostate cancer treatment. © 2009 Wiley-Liss, Inc.

Más información

Título según WOS: Regulation of Cell Survival by Resveratrol Involves Inhibition of NF kappa B-Regulated Gene Expression in Prostate Cancer Cells
Título según SCOPUS: Regulation of cell survival by resveratrol involves inhibition of NF?B-regulated gene expression in prostate cancer cells
Título de la Revista: Prostate
Volumen: 69
Número: 10
Editorial: Wiley
Fecha de publicación: 2009
Página de inicio: 1045
Página final: 1054
Idioma: English
URL: http://doi.wiley.com/10.1002/pros.20953
DOI:

10.1002/pros.20953

Notas: ISI, SCOPUS