Background: Studies have shown that supplementation of adult men with selenium-enriched yeast (SY) was protective against prostate cancer (PCa) and also reduced oxidative stress and levels of prostate-specific antigen. Here, we determined the effect of SY supplementation on global serum protein expression in healthy men to provide new insights into the mechanism of selenium chemoprevention; such proteins may also serve as biomarkers of disease progression. Methods: Serum samples from 36 adult men were obtained from our previous SY clinical trial, 9 months after supplementation with either SY (247 μg/d; n = 17) or placebo (nonenriched yeast; n = 19). Results: Proteomic profiling using two-dimensional difference in gel electrophoresis followed by liquid chromatography-tandem mass spectrometry revealed a total of 1,496 candidate proteins, of which, 11 were differentially expressed in the SY group as compared with placebo. Eight proteins were upregulated [clusterin isoform 1 (CLU), transthyretin, α-1B-glycoprotein, transferrin, complement component 4B proprotein, isocitrate dehydrogenase, haptoglobin, and keratin 1] and three proteins were downregulated [α-1 antitrypsin (AAT), angiotensin precursor, and albumin precursor] by SY. All of the identified proteins were redox-sensitive or involved in the regulation of redox status. Because both AAT and CLU have been previously linked to PCa development, their identities were confirmed by two-dimensional Western blot analysis. Conclusions: We identified AAT and CLU as potential candidate proteins involved in the mechanism of PCa prevention by SY. Collectively, proteins identified in this study might serve as potential new biomarkers for monitoring and comparing responses to selenium-based chemopreventive agents. Impact: Proteomic analysis of serum might be useful for the early detection and monitoring efficacy of chemopreventive agents.
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