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 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.
Papazisis
Konstantinos T
KT
Theagenion Cancer Institute, and Department of Biology, Medical Faculty, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece. konstantinos.papazisis@cancer.org.uk
Kalemi
Theodora G
TG
Zambouli
Dimitra
D
Geromichalos
George D
GD
Lambropoulos
Alexandros F
AF
Kotsis
Alexandros
A
Boutis
Lazaros L
LL
Kortsaris
Alexandros H
AH
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D016203:CDC2 Protein Kinase / Q000378:metabolism; D002166:Camptothecin / Q000008:administration & dosage; D002455:Cell Division / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004357:Drug Synergism; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D016195:G2 Phase / Q000187:drug effects; D019833:Genistein / Q000008:administration & dosage; D006367:HeLa Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D066298:In Vitro Techniques; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*
D019833:Genistein; D011505:Protein-Tyrosine Kinases; D016203:CDC2 Protein Kinase; D002166:Camptothecin