Abstract 4612: Cell-type dependent responses to selenium and knockdown of SBP2

Abstract

Abstract Selenium is a trace element essential for human health. Evidence from previous epidemiologic studies and clinical trials suggested that selenium is associated with prostate cancer prevention, but its failure in the Selenium and Vitamin E Cancer Prevention Trial (SELECT) to reduce prostate cancer incidence diminished its promise. The question of whether some patients could benefit from selenium supplementation while others might not demands a clearer understanding of selenium's mechanisms of action. One of the ways in which selenium acts as a chemopreventive agent is through incorporation into selenoproteins, which are antioxidant enzymes required to maintain redox homeostasis; however, selenoproteins’ large number and redundant functions make analyzing their effects on cellular functions difficult. Therefore, we recently targeted selenocysteine insertion sequence-binding protein 2 (SBP2), required for selenoprotein synthesis; knocked down SBP2 expression in different cell lines; and examined the effect on cell survival, cell cycle, and cell survival pathways. We found that knocking down SBP2 resulted in apoptosis in NIH/3T3 and HEK-293 cells, especially in the presence of H2O2. Interestingly abrogation of SBP2 function affected the level of p21 protein in a cell type-specific manner. Additionally, sodium selenite or seleno-methionine treatment led to distinct changes in p21 and p53 protein status in HEK-293, LNCaP, and DU145 cells. Molecular effects induced by knocking down SBP2 were cell-type dependent. Further studies involving a combinational approach are expected to contribute to understanding how selenium and selenoproteins mediate chemopreventive effects in prostate cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4612. doi:10.1158/1538-7445.AM2011-4612