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• W1487376377 endingPage "588" @default.
• W1487376377 startingPage "575" @default.
• W1487376377 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" @default.
• W1487376377 created "2016-06-24" @default.
• W1487376377 creator A5041766764 @default.
• W1487376377 creator A5048482314 @default.
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• W1487376377 date "2013-04-29" @default.
• W1487376377 modified "2023-09-25" @default.
• W1487376377 title "Homeostatic housecleaning effect of selenium: Evidence that noncytotoxic oxidant-induced damage sensitizes prostate cancer cells to organic selenium-triggered apoptosis" @default.
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• W1487376377 doi "https://doi.org/10.1002/biof.1106" @default.
• W1487376377 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/23625367" @default.
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