A role for peroxisome proliferator-activated receptor gamma in resveratrol-induced colon cancer cell apoptosis

Authors

  • Virginie Aires,

    1. Université de Bourgogne, Dijon, France
    2. Centre de Recherche INSERM U866 – Equipe Chimiothérapie, Métabolisme Lipidique et Réponse Immunitaire Antitumorale, Dijon, France
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  • Bertrand Brassart,

    1. Faculté des Sciences Exactes et Naturelles, Université de Reims Champagne Ardenne, Reims, France
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  • Annie Carlier,

    1. Faculté des Sciences Exactes et Naturelles, Université de Reims Champagne Ardenne, Reims, France
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  • Alessandra Scagliarini,

    1. Université de Bourgogne, Dijon, France
    2. Centre de Recherche INSERM U866 – Equipe Chimiothérapie, Métabolisme Lipidique et Réponse Immunitaire Antitumorale, Dijon, France
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  • Stéphane Mandard,

    1. Université de Bourgogne, Dijon, France
    2. Centre de Recherche INSERM U866 – Equipe Protéines de transfert des lipides et métabolisme des lipoprotéines, Dijon, France
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  • Emeric Limagne,

    1. Université de Bourgogne, Dijon, France
    2. Centre de Recherche INSERM U866 – Equipe Chimiothérapie, Métabolisme Lipidique et Réponse Immunitaire Antitumorale, Dijon, France
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  • Eric Solary,

    1. Inserm UMR 1009, Institut Gustave Roussy, Villejuif cedex, France
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  • Laurent Martiny,

    1. Faculté des Sciences Exactes et Naturelles, Université de Reims Champagne Ardenne, Reims, France
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  • Michel Tarpin,

    1. Faculté des Sciences Exactes et Naturelles, Université de Reims Champagne Ardenne, Reims, France
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  • Dominique Delmas

    Corresponding author
    1. Université de Bourgogne, Dijon, France
    2. Centre de Recherche INSERM U866 – Equipe Chimiothérapie, Métabolisme Lipidique et Réponse Immunitaire Antitumorale, Dijon, France
    • Correspondence: Dr. Dominique Delmas, Centre de Recherche Inserm U866 “Lipids, Nutrition, Cancer”, Faculty of Medicine 7, Bd Jeanne d’Arc, 21000 Dijon, France

      E-mail: ddelmas@u-bourgogne.fr

      Fax: +33-3-8039-3434

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Abstract

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.

Ancillary