Document Detail


Bortezomib and sphingosine kinase inhibitor interact synergistically to induces apoptosis in BCR/ABl(+) cells sensitive and resistant to STI571 through down-regulation Mcl-1.
MedLine Citation:
PMID:  21195056     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Interactions between the proteasome inhibitor, bortezomib, and the sphingosine kinase (SPK1) inhibitor, SKI, were examined in BCR/ABL human leukemia cells. Coexposure of K562 or chronic myeloid leukemia (CML) cells from patients to subtoxic concentrations of SKI (10μM) and bortezomib (100nM) resulted in a synergistic increase in caspase-3 cleavage and apoptosis. These events were associated with the downregulation of BCR-ABL and Mcl-1, and a marked reduction in SPK1 expression. In imatinib mesylate-resistant K562 cells that displayed decreased BCR-ABL expression, bortezomib/SKI treatment markedly increased apoptosis and inhibited colony-formation in association with the downregulation of Mcl-1. Finally, the bortezomib/SKI regimen also potently induced the downregulation of BCR/ABL and Mcl-1 in human leukemia cells. Collectively, these findings suggest that combining SKI and bortezomib may represent a novel strategy in leukemia, including apoptosis-resistant BCR-ABL(+) hematologic malignancies.
Authors:
Qing-Fang Li; Jun Yan; Kai Zhang; Yue-Feng Yang; Feng-Jun Xiao; Chu-Tse Wu; Hua Wang; Li-Sheng Wang
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2010-12-30
Journal Detail:
Title:  Biochemical and biophysical research communications     Volume:  -     ISSN:  1090-2104     ISO Abbreviation:  -     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2011-1-25     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0372516     Medline TA:  Biochem Biophys Res Commun     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2010 Elsevier Inc. All rights reserved.
Affiliation:
Department of Experimental Hematology, Beijing Institute of Radiation Medicine, 27 Taiping Road, Beijing 100850, PR China.
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