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Caspase- and p53-dependent apoptosis in breast carcinoma cells induced by a synthetic selenadiazole derivative
- Source :
-
Chemico-Biological Interactions . Jun2009, Vol. 180 Issue 1, p54-60. 7p. - Publication Year :
- 2009
-
Abstract
- Abstract: Selenadiazole derivative is one kind of synthetic organoselenium compounds with potent and broad-spectrum antitumor activity. In this study, we showed that anthrax [1,2-c] [1,2,5] selenadiazolo-6,11-dione (ASDO), an novel selenadiazole derivative, induced time- and dose-dependent apoptotic cell death in MCF-7 human breast carcinoma cells, as indicated by accumulation of sub-G1 cell population, DNA fragmentation, nuclear condensation, caspase activation and PARP cleavage. ASDO-induced apoptosis was significantly inhibited by a general caspase inhibitor z-VAD-fmk, demonstrating the important role of caspases in ASDO-induced apoptotic pathway. Treatment of MCF-7 cells with ASDO resulted in a rapid depletion of mitochondrial membrane potential and release of cytochrome c and Smac/Diablo through up-regulation of Bax, Bad and PUMA expression and down-regulation of Bcl-xl expression. Moreover, ASDO treatment up-regulated the expression levels of total p53 and its target gene p21Waf1. Silencing of p53 activation with RNA interference effectively blocked the ASDO-induced cell PARP cleavage, DNA fragmentation and caspase activation. Furthermore, ASDO-induced apoptosis was interestingly found to be independent of reactive oxygen species production. Taken together, we conclude that ASDO induces MCF-7 cell apoptosis through a p53-dependent and mitochondria-mediated pathway. [Copyright &y& Elsevier]
Details
- Language :
- English
- ISSN :
- 00092797
- Volume :
- 180
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Chemico-Biological Interactions
- Publication Type :
- Academic Journal
- Accession number :
- 38806332
- Full Text :
- https://doi.org/10.1016/j.cbi.2008.12.010