Document Detail

Synergistic effects of protein tyrosine kinase inhibitor genistein with camptothecins against three cell lines in vitro.
MedLine Citation:
PMID:  15893418     Owner:  NLM     Status:  MEDLINE    
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.
Konstantinos T Papazisis; Theodora G Kalemi; Dimitra Zambouli; George D Geromichalos; Alexandros F Lambropoulos; Alexandros Kotsis; Lazaros L Boutis; Alexandros H Kortsaris
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Publication Detail:
Type:  In Vitro; Journal Article    
Journal Detail:
Title:  Cancer letters     Volume:  233     ISSN:  0304-3835     ISO Abbreviation:  Cancer Lett.     Publication Date:  2006 Feb 
Date Detail:
Created Date:  2006-03-07     Completed Date:  2006-04-25     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  7600053     Medline TA:  Cancer Lett     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  255-64     Citation Subset:  IM    
Theagenion Cancer Institute, and Department of Biology, Medical Faculty, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece.
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MeSH Terms
Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
Apoptosis / drug effects
CDC2 Protein Kinase / metabolism
Camptothecin / administration & dosage
Cell Division / drug effects
Cell Proliferation / drug effects
Cells, Cultured
Drug Synergism
Fibroblasts / cytology,  drug effects*,  enzymology
G2 Phase / drug effects
Genistein / administration & dosage
Hela Cells / cytology,  drug effects,  enzymology
Ovarian Neoplasms / drug therapy*,  enzymology,  pathology
Phosphorylation / drug effects
Protein-Tyrosine Kinases / antagonists & inhibitors*
Reg. No./Substance:
446-72-0/Genistein; 7689-03-4/Camptothecin; EC Kinases; EC Protein Kinase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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