Author:
Fung Kim Y. C.,Cosgrove Leah,Lockett Trevor,Head Richard,Topping David L.
Abstract
Colorectal cancer (CRC) is a leading cause of preventable cancer deaths worldwide, with dietary factors being recognised as key risk modifiers. Foods containing dietary fibre are protective to a degree that the World Cancer Research Fund classifies the evidence supporting their consumption as ‘convincing’. The mechanisms by which fibre components protect against CRC remain poorly understood, especially their interactions with the gut microbiome. Fibre is a composite of indigestible plant polysaccharides and it is emerging that fermentable fibres, including resistant starch (RS), are particularly important. RS fermentation induces SCFA production, in particular, relatively high butyrate levels, andin vitrostudies have shown that this acid has strong anti-tumorigenic properties. Butyrate inhibits proliferation and induces apoptosis of CRC cell lines at physiological concentrations. These effects are attributed to butyrate's ability to alter gene transcription by inhibiting histone deacetylase activity. However, the more recent discovery of G-protein coupled receptors that bind butyrate and other SCFA and data obtained from proteomic and genomic experiments suggest that alternative pathways are involved. Here, we review the mechanisms involved in butyrate-induced apoptosis in CRC cells and, additionally, the potential role this SCFA may play in mediating key processes in tumorigenesis including genomic instability, inflammation and cell energy metabolism. This discussion may help to inform the development of strategies to lower CRC risk at the individual and population levels.
Publisher
Cambridge University Press (CUP)
Subject
Nutrition and Dietetics,Medicine (miscellaneous)
Cited by
257 articles.
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