Effects of resveratrol analogs on cell cycle progression, cell cycle associated proteins and 5fluoro-uracil sensitivity in human derived colon cancer cells

Authors

  • Didier Colin,

    1. Centre de Recherche Inserm 866, Dijon, France
    2. Faculté des Sciences Gabriel, Equipe Biochimie Métabolique et Nutritionnelle, Université de Bourgogne, Dijon, France
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  • Amandine Gimazane,

    1. Centre de Recherche Inserm 866, Dijon, France
    2. Faculté des Sciences Gabriel, Equipe Biochimie Métabolique et Nutritionnelle, Université de Bourgogne, Dijon, France
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  • Gérard Lizard,

    1. Centre de Recherche Inserm 866, Dijon, France
    2. Faculté des Sciences Gabriel, Equipe Biochimie Métabolique et Nutritionnelle, Université de Bourgogne, Dijon, France
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  • Jean-Claude Izard,

    1. Actichem, Montauban Cedex, France
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  • Eric Solary,

    1. Centre de Recherche Inserm 866, Dijon, France
    2. Faculté de Médecine, Centre de Recherche Inserm 866-Equipe Cancer et Différenciation, Université de Bourgogne, Dijon, France
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  • Norbert Latruffe,

    1. Centre de Recherche Inserm 866, Dijon, France
    2. Faculté des Sciences Gabriel, Equipe Biochimie Métabolique et Nutritionnelle, Université de Bourgogne, Dijon, France
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  • Dominique Delmas

    Corresponding author
    1. Centre de Recherche Inserm 866, Dijon, France
    2. Faculté des Sciences Gabriel, Equipe Biochimie Métabolique et Nutritionnelle, Université de Bourgogne, Dijon, France
    • Inserm U866, Centre de Recherche, LBMN, 6, Bd Gabriel, 21000 Dijon, France
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    • Fax: +33-3-80-39-62-50.


Abstract

Epidemiological studies suggested that trans-resveratrol, a wine grape component, could prevent malignant tumor development. This compound also demonstrated cytostatic and cytotoxic effects on tumor cells in vitro. To obtain trans-resveratrol derivatives with a better cellular uptake and enhanced antiproliferative effects, we synthesized a triacetate derivative as well as an oligomer, ε-viniferin and its acetylated form, ε-viniferin penta-acetate. We also obtained vineatrol, a wine grape shoot extract that associates several polyphenols that may act synergistically, including trans-resveratrol and ε-viniferin. We show here that resveratrol triacetate and vineatrol are as efficient as trans-resveratrol in inducing the accumulation of human colon cancer cells in early S phase of the cell cycle. This effect is associated with a nuclear redistribution of cyclin A and the formation of a cyclin A/cyclin-dependent kinase 2 complex whose kinase activity is increased. In contrast, ε-viniferin and its acetylated form do not demonstrate any significant activity on these cells when tested alone. Interestingly, resveratrol triacetate and vineatrol dramatically enhance 5-Fluoro-Uracil-mediated inhibition of colon cancer cell proliferation. Thus, acetylated derivatives of resveratrol have retained the cytostatic and cytotoxic activities of the parental molecule and thus deserve to be tested as chemosensitizers in animal models. © 2009 UICC

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