Abstract 4861: Identification of novel potential targets for selenomethionine-mediated chemoprevention in colorectal carcinoma mouse model via proteomics analysis.

Abstract

Abstract Despite some controversy, selenomethionine (SeMet) mediated protection against colorectal carcinoma (CRC) might be a very promising non-cytotoxic option. However, responsive molecular targets and underlying mechanisms of SeMet mediated chemoprevention are still unclear. Our aim was to discover new targets of SeMet mediated chemoprevention in CRC using proteomics analysis. We found dietary SeMet supplementation before carcinoma initiation effectively suppressed polyp incidence and dysplastic lesions without any adverse effects. To determine chemopreventive targets of SeMet, we employed 2-dimensional gel electrophoresis based proteomics analysis in CRC mouse model. Pretreatment with SeMet apparently modulated the expression of 30 proteins with functions in major processes like chronic inflammation, oxidative-stress and apoptosis as discovered through pathway analysis with Pathway studio software.We validated four proteins selected from pathway analysis including prohibitin, purine nucleoside phosphorylase, annexin 2 and c-reactive protein by immuno-histochemistry. 8-hydroxy-2′-deoxyguanosine (8-OHdG), a known oxidative stress marker was decreased by SeMet treatment in CRC mice as seen by immunohistochemistry. Further network analysis was done among these new four validated proteins, 8-OHdG and colorectal cancer. These four proteins found by proteomics analysis might be considered as potential chemopreventive biomarkers of SeMet against colon cancer and can help develop and improve approaches in preventive, therapeutic and prognostic aspects. Citation Format: Md. Mujibur Rahman, Jee Young Kwon, Young Rok Seo. Identification of novel potential targets for selenomethionine-mediated chemoprevention in colorectal carcinoma mouse model via proteomics analysis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4861. doi:10.1158/1538-7445.AM2013-4861