Suppression of azoxymethane-induced colon cancer development in rats by dietary resistant starch

Abstract

Resistant starch is a complex carbohydrate that reaches the colon where it can be fermented by the colonic microflora resulting in production of short chain fatty acids (SCFA), in particular butyrate. RS effects on colorectal tumorigenesis are contrasting and protection remains controversial. Butyrate has an important role as the preferred metabolic fuel and regulator of colonocyte proliferation, differentiation and apoptosis and may play a role in cancer prevention. Thus variation in butyrate production from different substrates might explain the variation in effect of RS. This study evaluated the hypothesis that feeding dietary resistant starch (as high amylose maize starch) would protect against azoxymethane (AOM)-colon carcinogenesis and favorably influence the colonic luminal environment. Male Sprague-Dawley rats (n = 90) were provided one of three diets: Control (without added dietary fibre or RS), 10% HAS (contained 100 g/kg raw high amylose maize starch) or 20% HAS (contained 200 g/kg high amylose maize starch). Rats were fed their experimental diets for four weeks after which they were injected with AOM (15 mg/kg) during the fifth and six week. Colons were resected (25 weeks post second injection) for evaluation of tumor formation, apoptosis, proliferating cell nuclear antigen (PCNA) labelling index and short chain fatty acid levels. Feeding resistant starch significantly reduced the incidence (p < 0.01) and multiplicity (p < 0.05) of adenocarcinomas in the colon compared to the Control diet. Both doses of HAS resulted in similar protection against colon tumorigenesis. Feeding RS significantly increased total SCFA concentrations, including butyrate in the distal colon. Apoptosis (p < 0.01) was also enhanced while PCNA labelling index was reduced (p < 0.01) in the distal colon with resistant starch feeding. The protective effect of consumption of RS as dietary high-amylose cornstarch against colon cancer development appears to be related to active fermentation in the colon, particularly through production of butyrate.

Role of Red Meat and Resistant Starch in Promutagenic Adduct Formation, MGMT Repair, Thymic Lymphoma and Intestinal Tumourigenesis in <b><i>Msh2</i></b>-Deficient Mice

“…Our findings support previous data [9,39,40] emphasising how RS can reduce the proliferation and DNA alkyl adducts in the distal colon of wild-type rodents. We have also shown that functioning Msh2 protects against hyperproliferation and ACF formation in the colon, and that RS consumption protects against colonic hyperproliferation caused by the genetic defect of MMR.…”

“…Antineoplastic properties identified in vitro and in vivo highlight the butyrate's ability to increase the removal of highly damaged colon cells via apoptosis, as well as reducing cellular proliferation of the distal colon to allow for repair processes [41,42,43]. These effects of butyrate imply that it is responsible for reducing ACF and colon tumours in genetically normal rodents [39,44] although no such reduction was evident in non-carcinogenic models of spontaneous CRC [32]. Reduction of hyperproliferation by RS was not seen in the proximal colon, and this could be due to the rapid formation of SCFAs once RS reaches the proximal colon from the caecum, with a steady decline in SCFAs further along the colon [45].…”

The Role of Bioactive Dietary Components in Modulating miRNA Expression in Colorectal Cancer

“…One mechanism through which high fiber diets decrease the risk of colon cancer is most likely due to increased production of butyrate by fermentation of dietary fiber in the intestine. Butyrate which is a short-chain fatty acid produced by dietary fiber fermentation in the colon is known as a chemoprotective agent [148]. …”

Cell kinetics and gene expression changes in colorectal cancer patients given resistant starch: a randomised controlled trial

“…There is compelling evidence that butyrate causes a dose-dependent suppression of proliferation of colon cancer cell lines,4 – 8 and RS has antineoplastic effects against colon cancer in animal models 9 – 11. Recent studies in rat have shown that feeding RS reduced the incidence and multiplicity of azomethane-induced colon cancers and reduced the tumour-enhancing effects of indigestible protein and red meat 12 – 14. These protective effects of RS were thought to be secondary to fermentation of RS to butyrate in the colon.…”