Adiponectin and Selenium: Role in chronic inflammation induced colon cancer

Le résumé fourni par la source

Inflammatory bowel diseases (IBD), ulcerative colitis (UC) and crohn's disease (CD), are associated with altered immune health with heightened mucosal inflammation and immune cell infiltration. IBD Patients, particularly UC patients, are at increased risk for colon cancer. Adiponectin (APN), an adipocytokine, is found in low levels in obese individuals. Its low level is considered a risk factor for colon cancer development. APN has been found to show anti-inflammatory and anti-cancerous properties. Moreover, Selenium (Se), an essential trace element with anti-oxidative properties, is a normal constituent of diet and has been investigated as a potential nutrient in the fight against cancer. In this study, we determined the effect of Se diet on the status of APN deficiency during chronic inflammation induced colon cancer (CICC). Inflammation and colon cancer were induced in both APN knockout (KO) and C57B1/6 wild type (WT) mice by 2% dextran sodium sulfate (DSS) and 1,2-Dimethylhydrazine (DMH) treatment respectively and were divided in-to eight treatment groups (n=9 per group): 1) control (no treatment) +Se; 2) control + normal diet; 3) treatment with three cycles of DSS (to induce chronic inflammation) + Se; 4) treatment with three cycles of DSS + normal diet; 5) weekly doses of DMH (20mg/kg of mouse body weight) for twelve weeks + Se; 6) weekly doses of DMH (20mg/kg of mouse body weight) for twelve weeks + normal diet; 7) a single dose of DMH followed by 3 cycles of DSS (DMH+DSS) (to evaluate chronic inflammation and the incidence of intestinal cancer) + Se; 8) a single dose of DMH followed by 3 cycles of DSS (DMH+DSS) + normal diet. Mice were observed for diarrhea, stool hemoccult, and weight loss and were sacrificed on day 192. Tumor area and number of polyps were measured. Tissue was collected from the tumor and non-tumor area of the colon for Western blot, immunohistochemistry, and gene analyses. Presence of Se in the diet, irrespective of genotype, had provided protection against DSS insult. APNKO mice were protected from DSS induced colitis during cycles 1, had a higher rate of epithelial cell proliferation and recovered from DSS insult earlier than their WT littermates. However, during the third DSS cycle, APNKO mice had significantly higher epithelial cell damage than WT mice as indicated by clinical score and showed greater number and larger area of tumors as compared to the WT counterpart. APNKO mice treated DSS+DMH were found to have significantly higher expression of pro-inflammatory and procancerous cytokines and proteins with lower expression of anti-inflammatory cytokines. Se diet protected against CICC in WT mice and to a lesser extent in APNKO mice, by reducing tumor number and area, and reduced expression of inflammatory and cancerous markers. Adiponectin deficiency contributes and aggravates the symptoms of CICC while Se diet provides protection against CICC and ameliorates its symptoms. Hence, APN in combination with Se in regular diet may play an important role in the prevention of colorectal cancer by modulating genes involved in chronic inflammation and tumorigenesis.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.