Effect of butyrate on APC-driven tumorigenesis

Author

Sonia Shahnaz

Date of Award

12-2000

Degree Type

Thesis

Degree Name

Master of Science

Major

Human Ecology

Major Professor

Jay Whelan

Committee Members

Naima Moustaid Moussa, Paula C. Zemel

Abstract

Butyrate is produced in the colon of mammals as a result of anaerobic fermentation of undigested fiber and has been found to be associated with the maintenance of colonic epithelium homeostasis. Studies have revealed that butyrate plays an important role in decreasing cellular proliferation, promoting differentiation, and inducing apoptosis in a number of colonic adenocarcinoma cell lines in vitro and thus provides a basis for investigators to hypothesize that butyrate might have antineoplastic properties against the development of colon cancer. The effects of butyrate on colon carcinogenesis in vivo studies still are not clearly delineated. Effects to demonstrate similar effects in vivo as observed in vitro have failed. This study investigated the role of butyrate in colonic adenocarcinoma cell lines that are defective in the APC gene (a tumor suppressor gene that is believed to be associated with the early stages of intestinal tumorigenesis) and the effect of dietary tributyrin (TB, triacylglycerol form of butyrate) on intestinal tumorigenesis in an experimental mouse model with a germ line mutation in the Apc gene. Apc^Min/+ mice develop most of their tumors in the small intestines, not in the colon, and thus provide an opportunity to determine whether butyrate is in fact the anti-tumor metabolite of dietary fiber. We demonstrated that butyrate has antiproliferative effects on SW480, SW620 and DLD-1 colonic tumor cell lines. Butyrate inhibited cell growth in a dose-dependent manner with marked reductions of 50-96% at doses between 2.5 and 1 0mM doses, similar to intracolonic concentrations found in vivo. Our in vivo study showed that the supplementation of TB to the Apc^Min/+ mice at a level of 6% of energy for 7 weeks failed to reduces tumor load in the colon or small intestines. It is evident that butyrate may be an important modifier or regulator of tumor cell growth in vitro, but its role as an antitumorigenic agent in vivo needs further investigation.

Recommended Citation

Shahnaz, Sonia, "Effect of butyrate on APC-driven tumorigenesis. " Master's Thesis, University of Tennessee, 2000.
https://trace.tennessee.edu/utk_gradthes/9488