Homeostatic housecleaning effect of selenium: Evidence that noncytotoxic oxidant-induced damage sensitizes prostate cancer cells to organic selenium-triggered apoptosis

Authors

  • Emily C. Chiang,

    1. Department of Nutrition Science, Purdue University, West Lafayette, IN
    2. Center on Aging and the Life Course, Purdue University, West Lafayette, IN
    3. Gerald P. Murphy Cancer Foundation, West Lafayette, IN
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  • David G. Bostwick,

    1. Bostwick Laboratories, Glen Allen, VA
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  • David J. Waters

    Corresponding author
    1. Center on Aging and the Life Course, Purdue University, West Lafayette, IN
    2. Gerald P. Murphy Cancer Foundation, West Lafayette, IN
    3. Department of Veterinary Clinical Sciences, Purdue University, West Lafayette, IN
    • Address correspondence to: David J. Waters, Ph.D., D.V.M., Director, Center for Exceptional Longevity Studies, Gerald P. Murphy Cancer Foundation, 3000 Kent Avenue Suite E2-100, West Lafayette, IN 47906, USA. E-mail: waters@purdue.edu Tel.: 765-775-1005; Fax: 765-775-1006;

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Abstract

The anti-cancer activity of organic selenium has been most consistently documented at supra-nutritional levels at which selenium-dependent, antioxidant enzymes are maximized in both expression and activity. Thus, there is a strong imperative to identify mechanisms other than antioxidant protection to account for selenium's anti-cancer activity. In vivo work in dogs showed that dietary selenium supplementation decreased DNA damage but increased apoptosis in the prostate, leading to a new hypothesis: Organic selenium exerts its cancer preventive effect by selectively increasing apoptosis in DNA-damaged cells. Here, we test whether organic selenium (methylseleninic acid; MSA) triggers more apoptosis in human and canine prostate cancer cells that have more DNA damage (strand breaks) created by hydrogen-peroxide (H2O2) at noncytotoxic doses prior to MSA exposure. Apoptosis triggered by MSA was significantly higher in H2O2-damaged cells. A supra-additive effect was observed—the extent of MSA-triggered apoptosis in H2O2-damaged cells exceeded the sum of apoptosis induced by MSA or H2O2 alone. However, neither the persistence of H2O2-induced DNA damage, nor the activation of mitogen-activated protein kinases was required to sensitize cells to MSA-triggered apoptosis. Our results document that selenium can exert a “homeostatic housecleaning” effect— a preferential elimination of DNA-damaged cells. This work introduces a new and potentially important perspective on the anti-cancer action of selenium in the aging prostate that is independent of its role in antioxidant protection. © 2013 BioFactors 39(5):575–588, 2013

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