Bile acids reduce the apoptosis-inducing effects of sodium butyrate on human colon adenoma (AA/C1) cells: Implications for colon carcinogenesis

Butyrate is produced in the colon by fermentation of dietary fibre and indu ces apoptosis in colon adenoma and cancer cell lines, which may contribute to the protective effect of a high fibre diet against colorectal cancer (CR C). However, butyrate is present in the colon together with unconjugated bi le acids, which are tumour promoters in the colon. We show here that bile a cids deoxycholate (DCA) and chenodeoxycholate (CDCA), at levels present in the colon, gave a modest increase in cell proliferation and decreased spont aneous apoptosis in AA/C1 adenoma cells. Bile acids significantly inhibited the induction of apoptosis by butyrate in AA/C1 cells. However, the surviv al-inducing effects of bile acids on AA/C1 cells could be overcome by incre asing the concentration of sodium butyrate. These results suggest that dysr egulation of apoptosis in colonic epithelial cells by dietary factors is a key factor in the pathophysiology of CRC. (C) 2000 Academic Press.