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Cancer Lett. 2006 Feb 28;233(2):255-64.

Synergistic effects of protein tyrosine kinase inhibitor genistein with camptothecins against three cell lines in vitro.

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Theagenion Cancer Institute, and Department of Biology, Medical Faculty, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece.


Genistein, a natural isoflavone product has been shown to induce cellular death and increase the apoptotic cell death induced by several DNA-damaging stimuli. We have explored the combined effect of genistein and camptothecins against three cell lines, HeLa (cervical cancer), OAW-42 (ovarian cancer) and L929 (normal fibroblasts). Combined effect was estimated in 96-well plates using the SRB method and median-effect analysis. Addition of genistein synergistically increased the antiproliferative affect of camptothecins, inhibiting the camptothecin-induced G2/M arrest and increasing the apoptotic cell population. In HeLa cells, genistein inhibited CDK1 phosphorylation after irinotecan treatment. Thus, abrogation of the G2/M checkpoint control by genistein may be a useful maneuver to increase cytotoxicity of agents that damage DNA and inhibit cell-cycle progression in the G2/M boundary.

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