RT Journal Article SR Electronic T1 Induction of Apoptosis by Staurosporine Involves the Inhibition of Expression of the Major Cell Cycle Proteins at the G2/M Checkpoint Accompanied by Alterations in Erk and Akt Kinase Activities JF Anticancer Research JO Anticancer Res FD International Institute of Anticancer Research SP 2893 OP 2898 VO 29 IS 8 A1 ANDREAS ANTONSSON A1 JENNY L. PERSSON YR 2009 UL http://ar.iiarjournals.org/content/29/8/2893.abstract AB Background: Staurosporine is a therapeutic agent that inhibits tumor cell growth by inducing cell death via intrinsic apoptotic pathways. Our previous studies in clinical settings have suggested that certain subpopulations of patients with acute myeloid leukemia (AML) had poor response to chemotherapy. Materials and Methods: The effect of staurosporine on apoptosis and cell cycle distribution in human leukemic cell line U-937 cells was determined. U-937 cells were treated with staurosporine at 0.5 μM for 18 hours or 1 μM for 24 hours. Analyses of cell cycle distribution and apoptosis were performed using flow cytometric analysis. The effects of staurosporine on the targeted proteins were assessed by immunoblot analysis. Results: A blockade of the cell cycle at the G2/M phase was observed in U-937 cells treated with staurosporine. A concomitant induction of apoptosis and activation of caspase-3 in U-937 cells was also achieved. Treatment of U-937 cells with staurosporine at 1 μM for 24 hours, compared with 0.5 μM for 18 hours, appeared to kill the leukemic more efficiently cells and this dose and duration may specifically target p27, Erk and Akt pathways that are important for cancer cell survival and resistance to treatment. We also show that the effects of stauroporine on cell cycle progression and apoptosis in U-937 cells are closely linked. Conclusion: Our results suggest that induction of apoptosis and inhibitory proliferation and survival pathways are important events induced by staurosporine. Understanding the conditions under which staurosporine shows high specificity and low toxicity in treatment of leukemic cells is of great importance for improving the efficacy of targeted therapeutics and overcoming resistance to chemotherapeutic agents.