Selenium is an essential micronutrient that is currently being tested for prostate cancer chemoprevention. In spite of its significant promise as a chemopreventive agent, the molecular mechanisms of selenium-mediated effects remain to be elucidated. Recent evidence suggests that selenium may mediate its chemopreventive effects by inducing apoptosis in human prostate cancer cells. Here we report that selenium-mediated apoptosis appears to involve membrane death receptor, DR5-dependent pathway in human prostate cancer cells. Selenium specifically upregulated DR5 expression but not that of DR4. Selenium upregulation of DR5 was coupled with caspase 8 activation and Bid cleavage thereby suggesting the existence of a potential cross-talk between the DR5 and the mitochondrial pathways. Thus, our results suggest that DR5 is specifically regulated by selenium and its activation may play an important role in selenium-mediated chemoprevention.
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He et al. (2002) studied this question.