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

• Published in: Cancer letters Vol. 233; no. 2; pp. 255 - 264
• Main Authors: Papazisis, Konstantinos T., Kalemi, Theodora G., Zambouli, Dimitra, Geromichalos, George D., Lambropoulos, Alexandros F., Kotsis, Alexandros, Boutis, Lazaros L., Kortsaris, Alexandros H.
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 28.02.2006; Elsevier Limited
• Subjects: Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Apoptosis; Apoptosis - drug effects; Camptothecin - administration & dosage; Camptothecins; CDC2 Protein Kinase - metabolism; Cell cycle; Cell Division - drug effects; Cell growth; Cell line; Cell Proliferation - drug effects; Cells, Cultured; Drug Synergism; Female; Fibroblasts - cytology; Fibroblasts - drug effects; Fibroblasts - enzymology; G2 Phase - drug effects; Genistein; Genistein - administration & dosage; HeLa Cells - cytology; HeLa Cells - drug effects; HeLa Cells - enzymology; Humans; In Vitro Techniques; Kinases; Ovarian Neoplasms - drug therapy; Ovarian Neoplasms - enzymology; Ovarian Neoplasms - pathology; Phosphorylation - drug effects; Protein-Tyrosine Kinases - antagonists & inhibitors; Synergism; Camptothecins; Cell line; Synergism; Genistein; Cell cycle; Apoptosis
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/j.canlet.2005.03.022

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 cell-cycle progression in the G 2/M boundary.