A role for peroxisome proliferator-activated receptor gamma in resveratrol-induced colon cancer cell apoptosis.
Fiche publication
Date publication
septembre 2014
Auteurs
Membres identifiés du Cancéropôle Est :
Pr DELMAS Dominique, Pr MARTINY Laurent, Pr TARPIN Michel, Dr BRASSART Bertrand, Dr AIRES Virginie, Dr LIMAGNE Emeric
Tous les auteurs :
Aires V, Brassart B, Carlier A, Scagliarini A, Mandard S, Limagne E, Solary E, Martiny L, Tarpin M, Delmas D
Lien Pubmed
Résumé
SCOPE: Resveratrol may function as a chemopreventive agent. A recent clinical study demonstrates a reduction in tumor cell proliferation in colorectal patients receiving repeated oral ingestion of resveratrol. However, gaps remain in our knowledge of the molecular mechanisms by which resveratrol exerts its chemopreventive effect. We have previously demonstrated that resveratrol induces apoptosis in colon cancer cells and that resveratrol can sensitize chemoresistant colon cancer cells to various drugs. Based on its ability to activate peroxisome proliferator-activated receptor gamma (PPARgamma) in colon cancer cells, we sought to determine the implication of this nuclear transcription factor in resveratrol-induced apoptosis. METHODS AND RESULTS: Transient transfection of cancer cells with a dominant-negative PPARgamma mutant or treatment with a PPARgamma antagonist (GW9662) reversed the inhibitory effect of resveratrol. Moreover, GW9662 prevented disruption of the cell cycle induced by resveratrol and consequently abrogated resveratrol-induced apoptosis. Tumor cell death was potentiated by combining resveratrol with rosiglitazone, a PPARgamma agonist. CONCLUSION: The results show that PPARgamma plays a role in resveratrol-induced apoptosis of colon carcinoma cells. The combination of resveratrol with a PPARgamma agonist could be a promising pharmacological approach for treatment of colorectal cancer.
Référence
Mol Nutr Food Res. 2014 Sep;58(9):1785-94