Premium
A role for peroxisome proliferator‐activated receptor gamma in resveratrol‐induced colon cancer cell apoptosis
Author(s) -
Aires Virginie,
Brassart Bertrand,
Carlier Annie,
Scagliarini Alessandra,
Mandard Stéphane,
Limagne Emeric,
Solary Eric,
Martiny Laurent,
Tarpin Michel,
Delmas Dominique
Publication year - 2014
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201300962
Subject(s) - resveratrol , peroxisome proliferator activated receptor , apoptosis , peroxisome proliferator activated receptor gamma , peroxisome proliferator , cancer research , peroxisome , receptor , colorectal cancer , chemistry , peroxisome proliferator activated receptor alpha , microbiology and biotechnology , cancer , nuclear receptor , medicine , biology , biochemistry , transcription factor , gene
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 (PPARγ) 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 PPARγ mutant or treatment with a PPARγ 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 PPARγ agonist. Conclusion The results show that PPARγ plays a role in resveratrol‐induced apoptosis of colon carcinoma cells. The combination of resveratrol with a PPARγ agonist could be a promising pharmacological approach for treatment of colorectal cancer.