THE NATURAL TYROSINE KINASE INHIBITOR GENISTEIN PRODUCES CELL-CYCLE ARREST AND APOPTOSIS IN JURKAT T-LEUKEMIA CELLS

Genistein, a natural isoflavonoid phytoestrogen, is a strong inhibitor of protein tyrosine kinases. We analyzed the effects of genistein on in vitro growth, cell-cycle progression and chromatin structure of Jur kat cells, a T-cell leukemia line with a constitutively increased tyro sine phosphorylation pattern. Exposure of in vitro cultured Jurkat cel ls to genistein resulted in a dose-dependent, growth inhibition. Cell- cycle analysis of genistein-treated cells revealed a G(2)/M arrest at low genistein concentrations (5-10 mu g/ml), while at higher doses (20 -30 mu g/ml) there was also a perturbation in S-phase progression. The derangements in cell-cycle control were followed by apoptotic death o f genistein-treated cells. Immunocytochemical analysis of cells staine d with a FITC-conjugated anti-phosphotyrosine monoclonal antibody show ed that 30 mu g/ml genistein effectively inhibit tyrosine kinase activ ity in cultured Jurkat cells. Our results indicate that the natural is oflavone genistein antagonizes tumor cell growth through both cell-cyc le arrest and induction of apoptosis and suggest that it could be a pr omising new agent in cancer therapy.