COMPARISON OF THE EFFECTS OF GENISTEIN AND AMSACRINE ON LEUKEMIA-CELLPROLIFERATION

Genistein is an inhibitor of the enzymes protein tyrosine kinase and t opoisomerase-II. It induces G(2)-phase arrest in human Jurkat and muri ne P388 leukemia cells at concentrations at which it is also cytotoxic . The effects of genistein have been investigated on Jurkat and P388 l eukemia sublines that manifest multidrug resistance. Cells that posses s altered topoisomerase-II activity (''atypical'' multidrug resistance ) are resistant to both the G(2) 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 class ical topoisomerase-II poison. This result identifies topoisomerase-II rather than tyrosine kinase activity as the target of genistein-mediat ed cytotoxicity and G(2)-phase arrest.