Comparison of the effects of genistein and amsacrine on leukemia cell proliferation.
Genistein is an inhibitor of the enzymes protein tyrosine kinase and topoisomerase-II. It induces G2-phase arrest in human Jurkat and murine P388 leukemia cells at concentrations at which it is also cytotoxic. The effects of genistein have been investigated on Jurkat and P388 leukemia sublines that manifest multidrug resistance. Cells that possess altered topoisomerase-II activity ("atypical" multidrug resistance) are resistant to both the G2 phase-arresting and cytotoxic effects of genistein. The ability of genistein to impede progression through the cell cycle and kill cells is similar to that of amsacrine, a classical topoisomerase-II poison. This result identifies topoisomerase-II rather than tyrosine kinase activity as the target of genistein-mediated cytotoxicity and G2-phase arrest.
Finlay
G J
GJ
Cancer Research Laboratory, University of Auckland School of Medicine, New Zealand.
Holdaway
K M
KM
Baguley
B C
BC
D000677:Amsacrine / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D018432:Drug Resistance, Multiple; D016195:G2 Phase / Q000187:drug effects; D019833:Genistein; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology*; D007941:Leukemia P388 / Q000188:drug therapy / Q000473:pathology; D007942:Leukemia, Experimental / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology*; D051379:Mice; D059005:Topoisomerase II Inhibitors; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D007529:Isoflavones; D059005:Topoisomerase II Inhibitors; D000677:Amsacrine; D019833:Genistein