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Induction of apoptosis by staurosporine involves the inhibition of expression of the major cell cycle proteins at the G(2)/m checkpoint accompanied by alterations in Erk and Akt kinase activities.

In English

Författare

Summary, in English

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 microM for 18 hours or 1 microM 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 G(2)/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 microM for 24 hours, compared with 0.5 microM 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.

Publiceringsår

2009

Språk

Engelska

Sidor

2893-2898

Publikation/Tidskrift/Serie

Anticancer research

Volym

29

Issue

8

Dokumenttyp

Artikel i tidskrift

Förlag

International Institute of Cancer Research

Ämne

  • Cancer and Oncology

Status

Published

Forskningsgrupp

  • Experimental Cancer Research, Malmö
  • Pathology, Malmö

ISBN/ISSN/Övrigt

  • ISSN: 1791-7530