title: Dietary selenium protects adiponectin knockout mice against chronic inflammation induced colon cancer.
abstract: Selenium (Se) is an essential dietary micronutrient that has been examined for protection against different types of cancers including colon cancer. Despite an established inverse association between Se and chronic inflammation induced colon cancer (CICC), the mechanistic understanding of Se's protective effects requires additional in-vivo studies using preclinical animal models of CICC. Adiponectin (APN) is an adipocytokine that is protective against CICC as well. However, its role in the anti-mutagenic effects of the Se-diet remains unknown. To address this knowledge gap, here we examine the ability of dietary Se in reducing CICC in APN knockout mice (KO) and its wild-type C57BL/6. CICC was induced with the colon cancer agent 1,2 dimethyl hydrazine (DMH) along with dextran sodium sulfate (DSS). Se-enhanced diet increased selenoproteins, Gpx-1 and Gpx-2, in the colon tissues, thereby reducing oxidative stress. Se-mediated reduction of CICC was evident from the histopathological studies in both mouse models. In both mice, reduction in inflammation and tumorigenesis associated well with reduced p65 phosphorylation and elevated 53 phosphorylation. Finally, we show that in both models Se-administration promotes goblet cell differentiation with a concomitant increase in the levels of associated proteins, Muc-2 and Math-1. Our findings suggest that Se's protection against CICC involves both colonic epithelial protection and anti-tumor effects that are independent of APN.
authors.affiliation: a Department of Exercise Science , Arnold School of Public Health, University of South Carolina , Columbia , SC , USA.
authors.forename: Arpit
authors.initials: A
authors.lastname: Saxena
authors.affiliation: a Department of Exercise Science , Arnold School of Public Health, University of South Carolina , Columbia , SC , USA.|b Center for Colon Cancer Research, University of South Carolina , Columbia , SC , USA.
authors.forename: Raja
authors.initials: R
authors.lastname: Fayad
authors.affiliation: a Department of Exercise Science , Arnold School of Public Health, University of South Carolina , Columbia , SC , USA.
authors.forename: Kamaljeet
authors.initials: K
authors.lastname: Kaur
authors.affiliation: a Department of Exercise Science , Arnold School of Public Health, University of South Carolina , Columbia , SC , USA.
authors.forename: Samantha
authors.initials: S
authors.lastname: Truman
authors.affiliation: a Department of Exercise Science , Arnold School of Public Health, University of South Carolina , Columbia , SC , USA.
authors.forename: Julian
authors.initials: J
authors.lastname: Greer
authors.affiliation: a Department of Exercise Science , Arnold School of Public Health, University of South Carolina , Columbia , SC , USA.|b Center for Colon Cancer Research, University of South Carolina , Columbia , SC , USA.
authors.forename: James A
authors.initials: JA
authors.lastname: Carson
authors.affiliation: b Center for Colon Cancer Research, University of South Carolina , Columbia , SC , USA.|c Department of Environmental Health Science , Arnold School of Public Health, University of South Carolina , Columbia , SC , USA.
authors.forename: Anindya
authors.initials: A
authors.lastname: Chanda
mesh_terms: D019813:1,2-Dimethylhydrazine / Q000633:toxicity; D052242:Adiponectin / Q000235:genetics*; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D063646:Carcinogenesis / Q000473:pathology; D002454:Cell Differentiation; D002471:Cell Transformation, Neoplastic / Q000473:pathology; D003093:Colitis, Ulcerative / Q000139:chemically induced / Q000150:complications* / Q000473:pathology; D003106:Colon / Q000473:pathology; D003110:Colonic Neoplasms / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D016264:Dextran Sulfate / Q000633:toxicity; D005979:Glutathione Peroxidase / Q000378:metabolism; D020397:Goblet Cells / Q000473:pathology; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018977:Micronutrients / Q000378:metabolism*; D055262:Mucin-2 / Q000378:metabolism; D016296:Mutagenesis; D009374:Neoplasms, Experimental / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D010766:Phosphorylation; D012643:Selenium / Q000378:metabolism*; D051996:Transcription Factor RelA / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D000094765:Glutathione Peroxidase GPX1
chemical_list: D019813:1,2-Dimethylhydrazine; D052242:Adiponectin; D051792:Basic Helix-Loop-Helix Proteins; D016264:Dextran Sulfate; D005979:Glutathione Peroxidase; D018977:Micronutrients; D055262:Mucin-2; D012643:Selenium; D051996:Transcription Factor RelA; D016159:Tumor Suppressor Protein p53; D000094765:Glutathione Peroxidase GPX1; C499919:Adipoq protein, mouse; C500943:Atoh1 protein, mouse; C524626:Muc2 protein, mouse; C498144:Rela protein, mouse; C492172:Gpx2 protein, mouse
keywords: Adiponectin; chronic inflammation; colon cancer; goblet cell differentiation; selenium