Resveratrol modulates roscovitine-mediated cell cycle arrest of human MCF-7 breast cancer cells

Human MCF-7 breast cancer cells are relatively resistant to anti-cancer drugs. Recently, we reported that roscovitine (ROSC), a selective cyclin-dependent kinase (CDK) inhibitor, arrested human MCF-7 breast cancer cells in G, phase of the cell cycle and concomitantly induced apoptosis. Moreover, we observed that the effect of the CDK inhibitor was dependent on the content of the culture medium. The cell cycle inhibiting action of ROSC was markedly diminished in human MCF-7 cells cultivated in medium supplemented with phenol red. These observations indicated that the therapeutic effects of ROSC can be affected by the components of the tissue medium. Recently, a number of epidemiological and experimental studies indicated that polyphenols (e.g. resveratrol, epicatechins etc.), abundant micronutrients in food, are anti-oxidant agents and could have strong anti-mitotic as well as pro-apoptotic activities. In the present contribution we raised the question whether the ROSC-mediated cell cycle arrest could be additionally modulated by compounds of natural origin, especially by polyphenols. Considering the potential benefits of the dietary components during the post-chemotherapy period, we focused our attention on the effects of resveratrol administration after treatment with ROSC. We analyzed whether the combined treatment with resveratrol would exert any additional effect on the cell cycle status of ROSC-treated human cancer cells. Resveratrol exhibited low direct cytotoxicity. The combined treatment with ROSC enhanced the ROSC-mediated inhibition of cell proliferation and cell cycle arrest. These results indicate that targeted combination of anti-cancer drugs with distinct naturally occurring compounds could increase the efficacy of the therapy and concomitantly reduce the undesired side effects exerted by cytostatic drugs. (c) 2007 Elsevier Ltd. All rights reserved.