Sodium butyrate induces apoptosis in human colonic tumour cell lines in a p53-independent pathway: implications for the possible role of dietary fibre in the prevention of large-bowel cancer.
The purpose of this study was to determine whether cultured colonic adenoma 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 originating from 6 colorectal adenomas and 7 carcinomas, spontaneous apoptosis was observed. Sodium butyrate, a naturally occurring fatty acid, is present in the human large bowel in millimolar amounts as a result of bacterial fermentation of dietary fibre. Sodium butyrate, at physiological concentrations, induced apoptosis in 2 adenoma cell lines, RG/C2 and AA/Cl, and in the carcinoma cell line PC/JW/FI. In contrast, transforming growth factor beta 1, which is thought to have an important role in the control of growth in colonic epithelium, did not induce apoptosis. Neither RG/C2 nor PC/JW/FI contain wild-type p53, therefore this tumour-suppressor gene is not required to mediate signals for the induction of apoptosis in colonic tumour cells. Our studies report the induction of apoptosis in colonic tumour cells by the naturally occurring fatty acid sodium butyrate. Since sodium butyrate is produced by bacterial fermentation of dietary fibre, the observation that this fatty acid can induce apoptosis could, in part, explain why a high-fibre diet appears to be protective against colon cancer. Escape from the induction of programmed cell death may be an important event in colorectal carcinogenesis.
Department of Pathology and Microbiology, University of Bristol, School of Medical Sciences, UK.
A
A
Hague
A M
AM
Manning
K A
KA
Hanlon
L I
LI
Huschtscha
D
D
Hart
C
C
Paraskeva
D000236:Adenoma / Q000235:genetics / Q000473:pathology*; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D002087:Butyrates / Q000494:pharmacology*; D020148:Butyric Acid; D002277:Carcinoma / Q000235:genetics / Q000473:pathology*; D003110:Colonic Neoplasms / Q000235:genetics / Q000473:pathology*; D004273:DNA, Neoplasm / Q000187:drug effects; D004043:Dietary Fiber / Q000494:pharmacology*; D016158:Genes, p53; D006801:Humans; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D002087:Butyrates; D004273:DNA, Neoplasm; D004043:Dietary Fiber; D016212:Transforming Growth Factor beta; D020148:Butyric Acid