title: Discovery of potential targets of selenomethionine-mediated chemoprevention in colorectal carcinoma mouse model using proteomics analysis.
abstract: Despite some controversy, selenomethionine (SeMet)-mediated protection against colorectal cancer (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 two-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 immunohistochemistry. 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.
authors.affiliation: Department of Life Science, Dongguk University-Seoul, 26 Pil-dong 3-ga, Jung-gu, Seoul 100-715, Republic of Korea.
authors.forename: Md Mujibur
authors.initials: MM
authors.lastname: Rahman
authors.forename: Young Rok
authors.initials: YR
authors.lastname: Seo
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D017209:Apoptosis; D001397:Azoxymethane / Q000009:adverse effects; D014408:Biomarkers, Tumor / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D018890:Chemoprevention; D003111:Colonic Polyps / Q000139:chemically induced / Q000473:pathology; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D016264:Dextran Sulfate / Q000009:adverse effects; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D015180:Electrophoresis, Gel, Two-Dimensional; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009363:Neoplasm Proteins / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress; D000091402:Prohibitins; D060066:Protein Interaction Maps; D020543:Proteome / Q000032:analysis*; D040901:Proteomics / Q000379:methods; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D012645:Selenomethionine / Q000008:administration & dosage / Q000627:therapeutic use*; D012984:Software
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D000091402:Prohibitins; D020543:Proteome; D012097:Repressor Proteins; D000080242:8-Hydroxy-2'-Deoxyguanosine; D002097:C-Reactive Protein; D016264:Dextran Sulfate; D012645:Selenomethionine; D003849:Deoxyguanosine; D001397:Azoxymethane