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Effects of resveratrol analogs on cell cycle progression, cell cycle associated proteins and 5fluoro‐uracil sensitivity in human derived colon cancer cells
Author(s) -
Colin Didier,
Gimazane Amandine,
Lizard Gérard,
Izard JeanClaude,
Solary Eric,
Latruffe Norbert,
Delmas Dominique
Publication year - 2009
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.24264
Subject(s) - resveratrol , chemistry , cell growth , cell cycle , acetylation , cancer research , biochemistry , cell , pharmacology , biology , gene
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