Abstract
Butyrate is produced in the colon of mammals as a result of microbial fermentation of dietary fiber, undigested starch, and proteins (Rombeau 1990). Butyrate may be an important protective agent in colonic carcinogenesis (Young 1994, Velázquez 1996a). Trophic effects on normal colonocytes in vitro (Scheppach 1992a) and in vivo (Velázquez 1996a) are induced by butyrate. In contrast, butyrate arrests the growth of neoplastic colonocytes and inhibits the preneoplastic hyperproliferation induced by some tumor promoters in vitro (Bartram 1994). Butyrate induces differentiation of colon cancer cell lines in culture (Young 1994). It also regulates the expression of molecules involved in colonocyte growth and adhesion, and inhibits the expression of several proto-oncogenes relevant to colorectal carcinogenesis, in vitro (Young 1994). Recent studies in our laboratory show that intraluminal butyrate treatments in normal rat colon results in proliferation patterns consistent with a potential protective role for butyrate in colon carcinogenesis (Velázquez 1996a). Associated with these effects, butyrate increased c-Jun whereas the secondary bile acid and tumor promoter, deoxycholate increased c-Fos, demonstrating for the first time, that these diet by-products can specifically affect colonic proto-oncogene expression in vivo. Moreover, we have recently observed that intravenous infusion of butyrate has significant anti-tumor effects, in an in vivo murine model of colon cancer metastatic to the liver (Velázquez 1996b). Preliminary work indicates that butyrate’s growth inhibitory effects in neoplastic colonocytes may be linked to inhibition of mevalonate-mediated cell growth. Additional studies are needed to fully evaluate butyrate’s anti-neoplastic effects in vivo, and to understand its mechanism(s) of action.