Document Detail


Bcl-2 overexpression attenuates SP600125-induced apoptosis in human leukemia U937 cells.
MedLine Citation:
PMID:  18343029     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
SP600125 is a specific inhibitor of c-Jun N-terminal kinase (JNK) that is known to strongly induce apoptosis and block cell cycle progression in G2/M phase. In this study, we demonstrated that treatment of U937 cells with SP600125 resulted in significant G2/M cell cycle arrest that was due to decreased cyclin B1 and cdc25c protein levels. Moreover, SP600125 promoted LDH release and DNA fragmentation that was associated with caspase-3 activation and degradation of its substrates. In contrast, overexpression of the antiapoptotic protein Bcl-2 rendered leukemia cells resistant to SP600125-induced apoptosis, but more sensitive to G2/M phase arrest and endoreduplication (>4N DNA). Overexpression of Bcl-2 significantly inhibited SP600125-induced caspase-3 activation and degradation of its substrates, and sustained expression levels of the IAP-2 proteins following SP600125 treatment. The inhibitory effect of Bcl-2 on apoptosis was attenuated by treatment with the small molecule Bcl-2 inhibitor, HA14-1. These data provide important mechanistic insights related to Bcl-2-mediated resistance to SP600125-induced apoptosis, and induction of G2/M phase arrest and endoreduplication.
Authors:
Dong-Oh Moon; Mun-Ock Kim; Yung Hyun Choi; Nam Deuk Kim; Jeong-Hyun Chang; Gi-Young Kim
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-03-14
Journal Detail:
Title:  Cancer letters     Volume:  264     ISSN:  0304-3835     ISO Abbreviation:  Cancer Lett.     Publication Date:  2008 Jun 
Date Detail:
Created Date:  2008-05-06     Completed Date:  2008-07-22     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  7600053     Medline TA:  Cancer Lett     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  316-25     Citation Subset:  IM    
Affiliation:
Faculty of Applied Marine Science, Cheju National University, Jeju Special Self-Governing Province 690-756, South Korea.
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MeSH Terms
Descriptor/Qualifier:
Anthracenes / pharmacology*
Apoptosis / drug effects*
Blotting, Western
Caspase 3 / drug effects,  metabolism
Cell Cycle / drug effects
DNA Fragmentation / drug effects
Enzyme Inhibitors / pharmacology*
Flow Cytometry
Humans
JNK Mitogen-Activated Protein Kinases / antagonists & inhibitors
Leukemia / metabolism*
Proto-Oncogene Proteins c-bcl-2 / biosynthesis*
U937 Cells
Up-Regulation
Chemical
Reg. No./Substance:
0/Anthracenes; 0/Enzyme Inhibitors; 0/Proto-Oncogene Proteins c-bcl-2; 0/anthra(1,9-cd)pyrazol-6(2H)-one; EC 2.7.11.24/JNK Mitogen-Activated Protein Kinases; EC 3.4.22.-/Caspase 3

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