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

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 G(2)/M arrest and increasing the apoptotic cell population. In HeLa cells, genistein inhibited CDK1 phosphorylation after irinotecan treatment. Thus, abrogation of the G(2)/M checkpoint control by genistein may be a useful maneuver to increase cytotoxicity of agents that damage DNA and inhibit cellcycle progression in the G(2)/M boundary. (c) 2005 Elsevier Ireland Ltd. All rights reserved.