title: Is resistant starch protective against colorectal cancer via modulation of the WNT signalling pathway?
abstract: Epidemiological and experimental evidence suggests that non-digestible carbohydrates (NDC) including resistant starch are protective against colorectal cancer. These anti-neoplastic effects are presumed to result from the production of the SCFA, butyrate, by colonic fermentation, which binds to the G-protein-coupled receptor GPR43 to regulate inflammation and other cancer-related processes. The WNT pathway is central to the maintenance of homeostasis within the large bowel through regulation of processes such as cell proliferation and migration and is frequently aberrantly hyperactivated in colorectal cancers. Abnormal WNT signalling can lead to irregular crypt cell proliferation that favours a hyperproliferative state. Butyrate has been shown to modulate the WNT pathway positively, affecting functional outcomes such as apoptosis and proliferation. Butyrate's ability to regulate gene expression results from epigenetic mechanisms, including its role as a histone deacetylase inhibitor and through modulating DNA methylation and the expression of microRNA. We conclude that genetic and epigenetic modulation of the WNT signalling pathway may be an important mechanism through which butyrate from fermentation of resistant starch and other NDC exert their chemoprotective effects.
authors.affiliation: Human Nutrition Research Centre,Institute of Cellular Medicine, Newcastle University,Newcastle upon Tyne NE4 5PL,UK.
authors.forename: Fiona C
authors.initials: FC
authors.lastname: Malcomson
authors.affiliation: Human Nutrition Research Centre,Institute of Cellular Medicine, Newcastle University,Newcastle upon Tyne NE4 5PL,UK.
authors.forename: Naomi D
authors.initials: ND
authors.lastname: Willis
authors.affiliation: Human Nutrition Research Centre,Institute of Cellular Medicine, Newcastle University,Newcastle upon Tyne NE4 5PL,UK.
authors.forename: John C
authors.initials: JC
authors.lastname: Mathers
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002087:Butyrates / Q000378:metabolism / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D003106:Colon / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D044127:Epigenesis, Genetic / Q000187:drug effects; D005232:Fatty Acids, Volatile / Q000096:biosynthesis; D006801:Humans; D011956:Receptors, Cell Surface / Q000378:metabolism; D013213:Starch / Q000494:pharmacology*; D060449:Wnt Signaling Pathway / Q000187:drug effects*; D043562:Receptors, G-Protein-Coupled
chemical_list: D000970:Antineoplastic Agents; D002087:Butyrates; D005232:Fatty Acids, Volatile; D011956:Receptors, Cell Surface; D013213:Starch; C473103:FFAR2 protein, human; D043562:Receptors, G-Protein-Coupled
keywords: ACF aberrant crypt foci; Butyrate; CRC colorectal cancer; Colorectal cancer; DMH dimethylhydrazine dihydrochloride; HAMS high-amylose maize starch; NDC non-digestible carbohydrates; Non-digestible carbohydrates; RS resistant starch; Resistant starch; SFRP secreted-frizzled related proteins; WNT signalling