Effect of short-chain fatty acids on the proliferation and differentiation of the human colonic adenocarcinoma cell line Caco-2.

ABSTRACT

OBJECTIVE: Short-chain fatty acids (SCFA) in the colon may maintain colonocyte differentiation and oppose carcinogenesis. The purpose of this study was to investigate the effects of three SCFA, butyrate, propionate and acetate, on the differentiation, proliferation, and matrix interactions of the Caco-2 human colonic adenocarcinoma cell line. METHODS: Differentiation was assessed by brush border enzyme expression and the doubling time (proliferation) was calculated directly from serial cell counts and by the logarithmic transformation method. Cell motility (migration) was quantitated by the expansion of a confluent Caco-2 monolayer (after release from a constraining fence) across bacteriologic plastic dishes precoated with saturating concentrations of type I collagen. Results were expressed as mean +/- SE and were analyzed by ANOVA and Bonferroni's modified t-test. RESULTS: All three SCFA studied altered the Caco-2 phenotype. Treatment with 10 mmol SCFA significantly prolonged the cell doubling time, promoted brush border enzyme expression (cathepsin C), and inhibited the motility of the Caco-2 cells. CONCLUSIONS: Butyrate, propionate and acetate inhibited the proliferation and motility of a well-differentiated human colonic cancer cell line while promoting the expression of the differentiation marker, cathepsin C. Thus the SCFA produced by bacterial fermentation of dietary fiber may exert a protective effect against the development of colon cancer.