Date of Award

2015

Document Type

Open Access Dissertation

Department

Exercise Science

First Advisor

Raja Fayad,

Abstract

Colon cancer is the second largest cause of cancer death in United States. Chronic inflammation and obesity predispose patients to colon cancer. Adipose tissue is a source of bioactive substances called adipokines. Adiponectin (APN), an adipokine has anti-inflammatory property and found at lower levels in obese patients. Selenium (Se), a trace mineral and a dietary supplement, is inversely associated with cancer risk and possess anti-inflammatory and anti-carcinogenic properties. The overall purpose of this dissertation is to determine if chronic inflammation leading to colon and intestinal cancer are regulated by APN or Se rich diet or both. The working hypothesis is that APN deficiency will decrease goblet cell mucous production in colon leading to greater chronic inflammation and exacerbate the clinical symptoms and tumor load related to colon cancer. Se rich diet alone or in combination with APN administration will increase goblet cell production and apoptosis of cancer cells leading to reduced clinical symptoms, tumor load and inflammation. The specific aim 1 studied the role of APN deficiency in chronic inflammation induced colon cancer (CICC) and its effect of goblet cell production. Absence of APN increased the severity of CICC and its administration on goblet cell lines decrease their apoptosis with increase Math-1 production and upregulated mucin (Muc-2) secretion through the activation of its receptors APN R1 and R2. Specific aim 2 was designed to study the effect of Se rich diet and APN deficiency in positive modulation of CICC. Our result indicated a sharp decline in the physical manifestations of colon cancer with Se rich diet and higher severity of CICC with APN deficiency providing another proof for the protective role of APN in CICC. Specific aim 3 studied the effect of APN administration or Se rich diet or both on intestinal cancer. We found a protective effect of Se, APN and both in reducing the clinical score and tumor load of intestinal cancer. Several mechanism of action of both Se and APN were studied in all the 3 aims. In conclusion, APN and Se could be used as a complimentary medicine in the treatment of colon and intestinal cancer.

Rights

© 2015, Arpit Saxena

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