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Death receptor 5 regulation during selenium-mediated apoptosis in human prostate cancer cells
Qin He1, Ayesha Rashid, Rong Rong
1Department of Pharmacology; SUNY Upstate Medical University; Syracuse, New York 13210 USA.
Abstract:
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.
Insights
Selenium may prevent prostate cancer by activating the DR5 death receptor pathway in cancer cells. This mechanism involves upregulating DR5 expression, leading to apoptosis and supporting selenium
Area of Science:
- Oncology
- Molecular Biology
- Nutritional Science
Background:
- Selenium is an essential micronutrient investigated for prostate cancer chemoprevention.
- The precise molecular mechanisms underlying selenium's chemopreventive effects are not fully understood.
- Emerging evidence suggests selenium may induce apoptosis in human prostate cancer cells.
Purpose of the Study:
- To elucidate the molecular mechanisms of selenium-mediated chemoprevention in prostate cancer.
- To investigate the role of death receptors, specifically DR5, in selenium-induced apoptosis.
Main Methods:
- Investigated selenium's effects on human prostate cancer cells.
- Analyzed the expression of death receptors DR5 and DR4.
- Assessed caspase 8 activation and Bid cleavage.
Main Results:
- Selenium specifically upregulated the expression of death receptor 5 (DR5), but not DR4.
- Selenium-induced DR5 upregulation was associated with caspase 8 activation and Bid cleavage.
- These findings suggest a link between the DR5 pathway and mitochondrial pathways in selenium's action.
Conclusions:
- DR5 is specifically regulated by selenium in human prostate cancer cells.
- Activation of the DR5 pathway is a key mechanism in selenium-mediated apoptosis.
- This pathway activation plays a significant role in selenium's potential as a prostate cancer chemopreventive agent.