The effects of short-chain fatty acids on colon epithelial proliferation and survival depend on the cellular phenotype.
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de Haro, Oscar
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AbstractPURPOSE: The short-chain fatty acids (SCFA) are produced via anaerobic bacterial fermentation of dietary fiber within the colonic lumen. Among them, butyrate is thought to protect against colon carcinogenesis. However, few studies analyze the effects of butyrate, and other SCFA, on normal epithelial cells and on epithelial regeneration during disease recovery. Since there are controversial in vitro studies, we have explored the effects of SCFA on different biological processes. METHODS: We used both tumoral (HT-29) and normal (FHC) epithelial cells at different phenotypic states. In addition, we analyzed the in vivo activity of soluble dietary fiber and SCFA production in the proliferation rate and regeneration of intestinal epithelial cells. RESULTS: The effect of butyrate on epithelial cells depends on the phenotypic cellular state. Thus, in nondifferentiated, high proliferative adenocarcinoma cells, butyrate significantly inhibited proliferation while increased differentiation and apoptosis, whereas other SCFA studied did not. However, in normal cells or in differentiated cultures as well as in in vivo studies, the normal proliferation and regeneration of damaged epithelium is not affected by butyrate or SCFA exposure. CONCLUSION: Although butyrate could exert antiproliferative effects in tumor progression, its production is safe and without consequences for the normal epithelium growth.
CitationJ. Cancer Res. Clin. Oncol. 2006, 132 (8):487-497
DescriptionDietary modulation of cancer & cancer biomarkers. Dietary item or component studied: short-chain fatty acids (SCFA)Outcome studied: proliferation rate and apoptosis in the adenocarcinoma cells; proliferation rate and regeneration of intestinal epithelial cells. Study type: human colon adenocarninoma cells (HT-29); fetal human normal colon cells (FHC); Female Wistar rats Tissue/biological material/sample size: rat colon. Mode of exposure: dietary. Impact on outcome (including dose-response):in nondifferentiated, high proliferative adenocarcinoma cells, butyrate significantly inhibited proliferation while increased differentiation and apoptosis, whereas other SCFA studied did not. However, in normal cells or in differentiated cultures as well as in in vivo studies, the normal proliferation and regeneration of damaged epithelium is not affected by butyrate or SCFA exposure.KEYWORDS - CLASIFFICATION: Adenocarcinoma;Alkaline Phosphatase;analysis;Animals;Apoptosis;Blotting,Western;Butyric Acid;Cell Proliferation;Cell Survival;Colonic Neoplasms;cytology;dietary modulation of cancer & cancer biomarkers;dietary modulation of carcinogenesis-related pathways;drug effects;enzymology;Epithelial Cells;Fatty Acids;Fatty Acids,Volatile;Female;HT29 Cells;Humans;Intestinal Mucosa;metabolism;pathology;pharmacology;Phenotype;prevention & control;Proliferating Cell Nuclear Antigen;Rats;Rats,Wistar;Research;Spain;