| Glycogen synthase kinase-3 (GSK-3) inhibition induces apoptosis in leukemic cells through mitochondria-dependent pathway. | |
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MedLine Citation:
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PMID: 22177455 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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The roles of glycogen synthase kinase-3 (GSK-3) in cell survival and apoptosis are controversial. We examined the effect of a specific GSK-3 inhibitor (SB-415286) on the regulation of leukemic cells proliferation and apoptosis. SB-415286 (40μM) induced cell growth inhibition, β-catenin stabilization, cell cycle arrest in G(2)/M phase, cyclin B1 downregulation, and apoptosis in leukemic cell lines KG1a, K562, and CMK. Blocking the death receptor pathway by using a specific inhibitor of caspase-8, did not inhibit SB-415286-induced apoptosis. This indicates that activation of caspase-8 is part of the intrinsic apoptotic pathway and occurs downstream of mitochondria membrane potential depolarization mediated by other caspases. Furthermore, we found that depolarization of mitochondria membrane caused by GSK-3 inhibition is regulated by dephosphorylation of anti-apoptotic protein Bcl-2 and downregulation of Bcl-xL. Thus, inhibition of GSK-3-induced apoptosis of leukemic cells could be an attractive target for treatment of leukemia. |
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Authors:
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Mohammad Reza Mirlashari; Ingrid Randen; Jens Kjeldsen-Kragh |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-12-15 |
Journal Detail:
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Title: Leukemia research Volume: - ISSN: 1873-5835 ISO Abbreviation: - Publication Date: 2011 Dec |
Date Detail:
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Created Date: 2011-12-19 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7706787 Medline TA: Leuk Res Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011 Elsevier Ltd. All rights reserved. |
Affiliation:
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Department of Immunology and Transfusion Medicine, Oslo University Hospital, Oslo, Norway. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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