Document Detail

SAHA treatment overcomes the anti-apoptotic effects of Bcl-2 and is associated with the formation of mature PML nuclear bodies in human leukemic U937 cells.
MedLine Citation:
PMID:  19631782     Owner:  NLM     Status:  MEDLINE    
Bcl-2 protects tumor cells from the apoptotic effects of various antineoplastic agents. Increased expression of Bcl-2 has been associated with poor response to chemotherapy in various malignancies, including leukemia. Therefore, bypassing the resistance conferred by anti-apoptotic factors such as Bcl-2 represents an attractive therapeutic strategy against cancer cells, including leukemic cells. We undertook this study to examine whether SAHA (suberoylanilide hydroxamic acid) overcomes the resistance by Bcl-2 in human leukemic cells, with a specific focus on the involvement of PML-NBs. Experiments were conducted with Bcl-2-overexpressing human leukemic U937 cells. Since we previously demonstrated that overexpression of Bcl-2 attenuates resveratrol-induced apoptosis in human leukemic U937 cells, resveratrol-treated U937 cells were used as a negative control. The present study indicates that SAHA at 1-7 microM, the dose range known to induce apoptosis in various cancer cells, overcomes the anti-apoptotic effects of Bcl-2 in Bcl-2-overexpressing human leukemic U937 cells. Notably, we observed that SAHA-induced formation of mature promyelocytic leukemia (PML) nuclear bodies (NBs) correlates with overcoming the anti-apoptotic effects of Bcl-2 in human leukemic U937 cells. Thus, PML protein and the formation of mature PML-NBs could be considered as therapeutic targets that could help bypass the resistance to apoptosis conferred by Bcl-2. Elucidating exactly how PML regulates Bcl-2 will require further work.
Jee Suk Lee; Seung Hun Jeong; Young Hwa Soung; Tae Hyun Kim; Hong Jo Choi; Bong Soo Park; Taeg Kyu Kwon; Young Hyun Yoo
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-02-23
Journal Detail:
Title:  Chemico-biological interactions     Volume:  181     ISSN:  1872-7786     ISO Abbreviation:  Chem. Biol. Interact.     Publication Date:  2009 Sep 
Date Detail:
Created Date:  2009-07-27     Completed Date:  2009-08-18     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0227276     Medline TA:  Chem Biol Interact     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  61-70     Citation Subset:  IM    
Department of Anatomy and Cell Biology, Dong-A University College of Medicine and Medical Science Research Center, 3-1 Dongdaesin-dong, Seo-gu, Busan, South Korea.
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MeSH Terms
Apoptosis / drug effects*,  physiology
Blotting, Western
Caspase 3 / metabolism
Electrophoresis, Polyacrylamide Gel
Fluorescent Antibody Technique
Hydroxamic Acids / pharmacology*
Intranuclear Inclusion Bodies / drug effects*
Leukemia / pathology
Membrane Potentials / drug effects
Microscopy, Confocal
Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors,  physiology*
U937 Cells
Reg. No./Substance:
0/Hydroxamic Acids; 0/Proto-Oncogene Proteins c-bcl-2; 149647-78-9/vorinostat; EC 3.4.22.-/Caspase 3

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