Journal
FREE RADICAL BIOLOGY AND MEDICINE
Volume 46, Issue 8, Pages 1186-1196Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2009.01.026
Keywords
Selenium; Bax; Apoptosis; Colorectal cancer; Chemotherapy; Free radicals
Funding
- Natural Science Foundation of China [2006CB910102, 2007CB507400, 30711080, 30700399, 30770491, 30370348]
- Beijing Natural Science Foundation [508201, 7032034]
- China for Doctor-Training Unit [20010023029]
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Emerging evidence suggests that selenium has chemotherapeutic potential by inducing cancer cell apoptosis with minimal side effects to normal cells. However, the mechanism by which selenium induces apoptosis is not well understood. We have investigated the role of Bax, a Bcl-2 family protein and a critical regulator of the mitochondrial apoptotic pathway, in selenite-induced apoptosis in colorectal cancer cells. We found that supranutritional doses of selenite could induce typical apoptosis in colorectal cancer cells in vitro and in xenograft tumors. Selenite triggers a conformational change in Bax, as detected by the 6A7 antibody, and leads to Bax translocation into the mitochondria, where Bax forms oligomers to mediate cytochrome c release. Importantly, we show that the two conserved cysteine residues of Bax seem to be critical for sensing the intracellular ROS to initiate Bax conformational changes and subsequent apoptosis. Our results show for the first time that selenite can activate the apoptotic machinery through redox-dependent activation of Bax and further suggest that selenite could be useful in cancer therapy. (C) 2009 Elsevier Inc. All rights reserved.
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