Bcl-2 attenuates anticancer agents-induced apoptosis by sustained activation of Akt/protein kinase B in U937 cells

Aberrant overexpression of antiapoptotic members of the Bcl-2 protein family contributes to resistance to anticancer therapeutic drugs. Thus, this protein represent attractive target for novel anticancer agents. In the present study, we determined the effect of the anti-apoptosis protein Bcl-2 on ca...

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Bibliographic Details
Published in:Apoptosis (London) 2005-12, Vol.10 (6), p.1333-1343
Main Authors: Woo, K J, Yoo, Y H, Park, J-W, Kwon, T K
Format: Article
Language:English
Subjects:
Antineoplastic Agents - pharmacology
Apoptosis
Apoptosis - drug effects
Caspase 3 - metabolism
Ceramides - pharmacology
Chromones - pharmacology
Enzyme Activation - drug effects
Enzyme Inhibitors - pharmacology
Flavonoids - pharmacology
Genetic Vectors
Humans
Inactivation
Inhibitor of Apoptosis Proteins - metabolism
Kinases
Kinetics
Morpholines - pharmacology
Phosphatidylinositol 3-Kinases - antagonists & inhibitors
Phosphorylation - drug effects
Protein-Serine-Threonine Kinases - metabolism
Proteins
Proto-Oncogene Proteins c-akt - antagonists & inhibitors
Proto-Oncogene Proteins c-akt - metabolism
Proto-Oncogene Proteins c-bcl-2 - metabolism
Time Factors
U937 Cells
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Summary:Aberrant overexpression of antiapoptotic members of the Bcl-2 protein family contributes to resistance to anticancer therapeutic drugs. Thus, this protein represent attractive target for novel anticancer agents. In the present study, we determined the effect of the anti-apoptosis protein Bcl-2 on caspase-3 activation, PLC-gamma1 degradation and Akt activation during the various anticancer agents-induced apoptosis. Treatment with chrysin for 12 h produced morphological features of apoptosis in U937 cells, which was associated with caspase-3 activation and PLC-gamma1 degradation. Induction of apoptosis was also accompanied by down-regulation of XIAP and inactivation of Akt. Chrysin-induced caspase-3 activation, PLC-gamma1 degradation and apoptosis were significantly attenuated in Bcl-2 overexpressing U937/Bcl-2 cells. Ectopic expression of Bcl-2 appeared to inhibit ceramide-, and Akt specific inhibitor (SH-6)-induced apoptosis by sustained Akt activation. Thus, our findings imply that some of the biological functions of Bcl-2 may be attributed to their ability to inhibit anticancer agents-induced apoptosis through the sustained Akt activation.
ISSN:1360-8185
1573-675X
DOI:10.1007/s10495-005-2763-5