Effects of Curcumin and Genistein on MCT1 Expression in Cancer Cells

Grant Winner

Dean

Abstract

High fiber diet has been frequently reported to be beneficial for maintaining the health of colon tissues. Dietary fiber, proteins, and resistant starch escaping hydrolysis in the small intestine are fermented by colonic microflora to form short chain fatty acids (SCFA) such as acetate, propionate, and butyrate. These monocarboxylate weak acids comprise the majority of the anions and the osmolytes in the colonic lumen and contribute to several colonic epithelial cell activities. Among the aforementioned SCFAs butyrate has been shown to be the most important for maintaining the health of colonic mucosa because, it is the preferred metabolic fuel providing about 60% of the colonocytes' energy requirements. Several in vivo studies have correlated butyrate levels with decreased incidence of colon cancer. Essential to this protective role is the absorption of butyrate across the colonic luminal membrane into colonocytes. The carrier protein that transports butyrate across the colonic luminal membrane is monocarboxylate transporter 1 (MCT1) which is an important member of the monocarboxylate transporters. Curcumin, the major yellow pigment present in turmeric is commonly used as a coloring and flavoring additive in foods. Recent studies have indicated that dietary administration of curcumin may have beneficial effects in various diseases conditions including colon cancer. Genistein is one of the isoflavones normally found in soybeans that has been shown to produce antiproliferative and proapoptotic effects in various types of cancer cells. Recently we have identified the beneficial effects of curcumin and genistein on MCT1 expression which in turn could minimize the colon cancer risk. To confirm our initial findings, the effect of curcumin and genistein on MCT1 mRNA expression will be studied in Caco2 cells (colo rectal epithelial cells) in a wide range of concentrations (1 uM to 50 uM). The results from this study will indicate, for the first time, the effects of curcumin and genistein on MCT1 mRNA expression in colonocytes. The results obtained from the proposed study could be used as preliminary data for obtaining exploratory grants such as R03 from NIH.