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 (H2 O2 ) 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 H2 O2 -damaged cells exceeded the sum of apoptosis induced by MSA or H2 O2 alone. However, neither the persistence of H2 O2 -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.
Written by:
Chiang EC, Bostwick DG, Waters DJ. Are you the author?
Department of Nutrition Science, Purdue University, West Lafayette, IN; Center on Aging and the Life Course, Purdue University, West Lafayette, IN; Gerald P. Murphy Cancer Foundation, West Lafayette, IN.
Reference: Biofactors. 2013 Apr 29. Epub ahead of print.
doi: 10.1002/biof.1106
PubMed Abstract
PMID: 23625367
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