Epidemiological and clinical intervention studies support the protective role of selenium against development of prostate cancer. However, the mechanisms by which selenium inhibits prostate cancer remain unclear. In a clinical pilot study, the serum proteomic profiles of eight individuals from selenized-yeast (240 μg/day) supplemented group and equal number from the placebo group receiving regular yeast were compared. Serum samples were depleted of the six most abundant proteins (including albumin and IgG) and labeled with Cy5 or Cy3. Equal aliquots of each sample were also pooled and labeled with Cy2 and used as internal standard. Cy5 and Cy3-labeled samples were separated by two-dimensional difference in-gel electrophoresis (2D-DIGE) and the differences in levels of candidate protein spot features were determined by DeCyder software analysis. Several of the differentially expressed spots were excised, trypsin digested and analyzed by MALDI/TOF/TOF. Thirteen differentially expressed proteins were identified including pre-serum amyloid P component (PSAPC) and alpha-1-antitrypsin (AAT). These proteins were further analyzed by 2D-western blot analysis. PSAPC protein level was increased and AAT protein expression was decreased in serum of individuals supplemented with selenized-yeast for nine-months when compared to the placebo group. Levels of AAT have recently been shown to correlate with PSA levels in sera of prostate cancer patients. Previously we have reported down regulation of PSA in selenized-yeast supplemented individuals. Our results suggest that in addition to PSA, AAT may be used as a biomarker for selenium response. Support for the current studies provided by CA 29502 (RS) and Penn State Cancer Institute Funds.

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA