RESUMEN
Natural phytoestrogens such as the isoflavones genistein and daidzein, and the flavones quercetin exhibit anti-cancer properties. This study was purpose to investigate the anti-proliferative effect of phytoestrogens on acute myeloid leukemia (AML) and chronic myeloid leukemia (CML) cells, and their synergistic antileukemic effect in combination with chemotherapeutic drugs. Optimal dosage of genistein, quercetin and in combination with chemicals for leukemia cells were determined by experiments. Cell viability, apoptosis induction and cell cycle arrest were detected by trypan blue staining, MTT assay, optical microscopy, flow cytometry (FCM). The schedule treatment of combination of genistein and chemicals was determined. The results showed that genistein exhibited a dose- and time-dependent inhibitory effect on cell proliferation in NB4 and HL-60 cells, induced apoptosis and cell cycle arrest in G2/M phase. Quercetin had evident inhibitory effect on the proliferation of K562 and K562/A cells. The combination of genistein and chemicals exerted a synergistic effect on cell growth inhibition. In conclusion, this study demonstrated the synergistic antileukemic effect of genistein with chemotherapeutic drugs on leukemic cells. This combination appears to be a new idea for the clinical novel treatment of leukemia.
Asunto(s)
Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Leucemia Monocítica Aguda/patología , Leucemia Mieloide Aguda/patología , Fitoestrógenos/farmacología , Proliferación Celular/efectos de los fármacos , Sinergismo Farmacológico , Genisteína/farmacología , Células HL-60 , Humanos , Isoflavonas/farmacología , Quercetina/farmacologíaRESUMEN
Genistein (GEN) is a natural protein tyrosine kinase inhibitor. We analyzed the molecular response of HL-60 cells to GEN treatment by gel-based proteomics approach. Fourteen differentially expressed proteins which are functionally involved in metabolism, cell signaling, RNA processing, cell proliferation and motility, and chaperones were identified. Both the dose- and time-dependent up-regulation of Hsp70 protein 8 and heterogeneous nuclear ribonucleoprotein (hnRNP) H1, and the down-regulation of Rab14, hnRNP C and stathmin-1 by GEN were verified by immunoblot analysis. Our novel findings provide insightful clues to the potential therapeutic targets for leukemia treatment in diverse tyrosine kinase-dependent cellular pathways.