Discovery of potential targets of selenomethionine mediated chemoprevention in colorectal carcinoma mouse model using proteomics analysis

Menée à l'aide d'un modèle murin et à l'aide d'une analyse protéomique, cette étude identifie, dans le cadre de la chimioprévention d'un carcinome colorectal par la sélénométhionine, quatre biomarqueurs impliqués dans les processus pro- ou anti-inflammatoires

Résumé en anglais

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.