Spinozzi F, Pagliacci M C, Migliorati G, Moraca R, Grignani F, Riccardi C, Nicoletti I
Istituti di Medicina Interna e Scienze Oncologiche, Università di Perugia, Italy.
Leuk Res. 1994 Jun;18(6):431-9. doi: 10.1016/0145-2126(94)90079-5.
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 Jurkat cells, a T-cell leukemia line with a constitutively increased tyrosine phosphorylation pattern. Exposure of in vitro cultured Jurkat cells to genistein resulted in a dose-dependent, growth inhibition. Cell-cycle analysis of genistein-treated cells revealed a G2/M arrest at low genistein concentrations (5-10 micrograms/ml), while at higher doses (20-30 micrograms/ml) there was also a perturbation in S-phase progression. The derangements in cell-cycle control were followed by apoptotic death of genistein-treated cells. Immunocytochemical analysis of cells stained with a FITC-conjugated anti-phosphotyrosine monoclonal antibody showed that 30 micrograms/ml genistein effectively inhibit tyrosine kinase activity in cultured Jurkat cells. Our results indicate that the natural isoflavone genistein antagonizes tumor cell growth through both cell-cycle arrest and induction of apoptosis and suggest that it could be a promising new agent in cancer therapy.
染料木黄酮是一种天然的异黄酮类植物雌激素，是蛋白酪氨酸激酶的强效抑制剂。我们分析了染料木黄酮对Jurkat细胞体外生长、细胞周期进程和染色质结构的影响，Jurkat细胞是一种T细胞白血病细胞系，其酪氨酸磷酸化模式持续增加。将体外培养的Jurkat细胞暴露于染料木黄酮会导致剂量依赖性的生长抑制。对经染料木黄酮处理的细胞进行细胞周期分析发现，在低浓度染料木黄酮（5 - 10微克/毫升）下细胞停滞于G2/M期，而在较高剂量（20 - 30微克/毫升）时，S期进程也受到干扰。细胞周期控制紊乱之后，经染料木黄酮处理的细胞发生凋亡性死亡。用异硫氰酸荧光素（FITC）偶联的抗磷酸酪氨酸单克隆抗体对细胞进行免疫细胞化学分析表明，30微克/毫升的染料木黄酮能有效抑制培养的Jurkat细胞中的酪氨酸激酶活性。我们的结果表明，天然异黄酮染料木黄酮通过细胞周期停滞和诱导凋亡来拮抗肿瘤细胞生长，并提示它可能是癌症治疗中有前景的新型药物。
