SODIUM-BUTYRATE INDUCES APOPTOSIS IN HUMAN COLONIC TUMOR-CELL LINES IN A P53-INDEPENDENT PATHWAY - IMPLICATIONS FOR THE POSSIBLE ROLE OF DIETARY FIBER IN THE PREVENTION OF LARGE-BOWEL CANCER

The purpose of this study was to determine whether cultured colonic ad enoma and carcinoma cells undergo apoptosis (programmed cell death) in vitro and whether specific growth and dietary factors, thought to be involved in the control of growth and differentiation of human colonic cells, could induce cell death through apoptosis. In cell lines origi nating from 6 colorectal adenomas and 7 carcinomas, spontaneous apopto sis was observed. Sodium butyrate, a naturally occurring fatty acid, i s present in the human large bowel in millimolar amounts as a result o f bacterial fermentation of dietary fibre. Sodium butyrate, at physiol ogical concentrations, induced apoptosis in 2 adenoma cell lines, RG/C 2 and AA/C1, and in the carcinoma cell line PC/JW/F1. In contrast, tra nsforming growth factor beta1, which is thought to have an important r ole in the control of growth in colonic epithelium, did not induce apo ptosis. Neither RG/C2 nor PC/JW/F1 contain wild-type p53, therefore th is tumour-suppressor gene is not required to mediate signals for the i nduction of apoptosis in colonic tumour cells. Our studies report the induction of apoptosis in colonic tumour cells by the naturally occurr ing fatty acid sodium butyrate. Since sodium butyrate is produced by b acterial fermentation of dietary fibre, the observation that this fatt y acid can induce apoptosis could, in part, explain why a high-fibre d iet appears to be protective against colon cancer. Escape from the ind uction of programmed cell death may be an important event in colorecta l carcinogenesis. (C) 1993 Wiley-Liss, Inc.