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http://dx.doi.org/10.5352/JLS.2007.17.4.552

Effects of Bcl-2 Overexpressing on the Apoptotic Cell Death Induced by HDAC Inhibitors in Human Leukemic U937 Cells  

Lee, In-Hyuk (Departments of Anatomy, Dongeui University College of Oriental Medicine)
Hur, Man-Gyu (Departments of Internal Medicine, Dongeui University College of Oriental Medicine)
Park, Dong-Il (Departments of Internal Medicine, Dongeui University College of Oriental Medicine)
Choi, Byung-Tae (Departments of Anatomy, Dongeui University College of Oriental Medicine)
Choi, Yung-Hyun (Departments of Biochemistry, Dongeui University College of Oriental Medicine and Department of Biomaterial Control(BK2l Program), Dongeui University Graduate School)
Publication Information
Journal of Life Science / v.17, no.4, 2007 , pp. 552-560 More about this Journal
Abstract
Histone deacetylase (HDAC) is overexpressed in a variety of cancers and is closely correlated with oncogenic factors. HDAC inhibitors such as trichostatin A(TSA) and sodium butyrate (Na-B) have been shown to induce apoptosis in vitro and in vivo in many cancer cells. The anti-apoptotic Bcl-2 protein has the remarkable ability to prevent cell death and Bcl-2 overexpression has been reported to protect against cell death. We previously reported that the apoptotic cell death of human leukemic U937 cells by TSA and Na-B treatment was associated with the down-regulation of Bcl-2 expression and activation of caspases. In the present study, we investigated the effects of Bcl-2 overexpression on the growth inhibition, cell cycle arrest and apoptosis induced by TSA and Na-B in U937 cells. TSA-induced growth inhibition, cell cycle arrest and apoptosis were significantly attenuated in Bcl-2 overexpressing U937/Bcl-2 cells however Na-B did not affected. Induction of apoptosis by TSA was accompanied by down-regulation of Bcl-2 expression, activation of caspase-3, -8 and -9, and degradation of DNA fragmentation factor/inhibitor of caspase-activated DNase, which was blocked by the overexpression of Bcl-2. Collectively, these findings suggest that ectopic expression of Bcl-2 appeared to inhibit TSA-induced apoptosis by interfering with inhibition of Bcl-2 and caspase activation.
Keywords
HDAC inhibitor; U937; apoptosis; Bcl-2; caspase;
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