Dietary selenium protects adiponectin knockout mice against chronic inflammation induced colon cancer

Arpit Saxena, Raja Fayad, Kamaljeet Kaur, Samantha Truman, Julian Greer, James Carson, Anindya Chanda

Research output: Contribution to journalArticle

2 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)257-267
Number of pages11
JournalCancer Biology and Therapy
Volume18
Issue number4
DOIs
StatePublished - Apr 3 2017

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Adiponectin
Selenium
Knockout Mice
Colonic Neoplasms
Inflammation
Phosphorylation
Antimutagenic Agents
Selenoproteins
1,2-Dimethylhydrazine
Diet
Dextran Sulfate
Adipokines
Goblet Cells
Micronutrients
Cell Differentiation
Colon
Carcinogenesis
Oxidative Stress
Animal Models

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Oncology
  • Pharmacology
  • Cancer Research

Cite this

Dietary selenium protects adiponectin knockout mice against chronic inflammation induced colon cancer. / Saxena, Arpit; Fayad, Raja; Kaur, Kamaljeet; Truman, Samantha; Greer, Julian; Carson, James; Chanda, Anindya.

In: Cancer Biology and Therapy, Vol. 18, No. 4, 03.04.2017, p. 257-267.

Research output: Contribution to journalArticle

Saxena, Arpit ; Fayad, Raja ; Kaur, Kamaljeet ; Truman, Samantha ; Greer, Julian ; Carson, James ; Chanda, Anindya. / Dietary selenium protects adiponectin knockout mice against chronic inflammation induced colon cancer. In: Cancer Biology and Therapy. 2017 ; Vol. 18, No. 4. pp. 257-267.
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