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 induces apoptosis in colon adenoma and cancer cell lines, which may contribute to the protective effect of a high fibre diet against colorectal cancer (CRC). However, butyrate is present in the colon together with unconjugated bile acids, which are tumour promoters in the colon. We show here that bile acids deoxycholate (DCA) and chenodeoxycholate (CDCA), at levels present in the colon, gave a modest increase in cell proliferation and decreased spontaneous apoptosis in AA/C1 adenoma cells. Bile acids significantly inhibited the induction of apoptosis by butyrate in AA/C1 cells. However, the survival-inducing effects of bile acids on AA/C1 cells could be overcome by increasing the concentration of sodium butyrate. These results suggest that dysregulation of apoptosis in colonic epithelial cells by dietary factors is a key factor in the pathophysiology of CRC.
McMillan
L
L
Department of Immunology, Birmingham University, Birmingham, B15 2TT, United Kingdom.
Butcher
S
S
Wallis
Y
Y
Neoptolemos
J P
JP
Lord
J M
JM
D000236:Adenoma / Q000178:diet therapy / Q000209:etiology / Q000473:pathology*; D017209:Apoptosis / Q000187:drug effects*; D001647:Bile Acids and Salts / Q000494:pharmacology*; D002087:Butyrates / Q000037:antagonists & inhibitors* / Q000494:pharmacology* / Q000627:therapeutic use; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002635:Chenodeoxycholic Acid / Q000494:pharmacology; D015179:Colorectal Neoplasms / Q000178:diet therapy / Q000209:etiology / Q000473:pathology*; D004247:DNA / Q000096:biosynthesis; D003840:Deoxycholic Acid / Q000494:pharmacology; D004043:Dietary Fiber / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D006801:Humans; D013997:Time Factors; D014407:Tumor Cells, Cultured
D001647:Bile Acids and Salts; D002087:Butyrates; D004043:Dietary Fiber; D003840:Deoxycholic Acid; D002635:Chenodeoxycholic Acid; D004247:DNA