Dietary resistant starch type 3 prevents tumor induction by 1,2-dimethylhydrazine and alters proliferation, apoptosis and dedifferentiation in rat colon.
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AbstractSome epidemiological and experimental studies suggest that consumption of resistant starch is preventive against colon cancer. Resistant starch leads to a fermentation-mediated increase in the formation of short-chain fatty acids, with a particularly high butyrate fraction in large bowel. Butyrate is considered to be protective against colon cancer because it causes growth arrest and apoptosis and regulates expression of proteins involved in cellular dedifferentiation in various tumor cell lines in culture. We sought to investigate these processes under conditions of a carcinogenicity experiment in vivo. In the present study, 1,2-dimethylhydrazine-treated Sprague-Dawley rats were fed standard diet (n=12) or diet with 10% hydrothermally modified Novelose 330, a resistant starch type 3 (RS3), replacing digestible starch (n=8). After 20 weeks tumor number, epithelial proliferation, apoptosis, immunoreactivity of carcinogenesis-related proteins [protein kinase C-delta (PKC-delta), heat shock protein 25 (HSP25) and gastrointestinal glutathione peroxidase (GI-GPx)], as well as mucin properties were evaluated in proximal and distal colon in situ. No tumors developed under RS3 diet, compared to a tumor incidence of 0.6+/-0.6 (P<0.05) under the standard diet. RS3 decreased the number of proliferating cells, the length of the proliferation zone and the total length of the crypt in the distal colon, but not proximal colon, and enhanced apoptosis in both colonic segments. It induced PKC-delta and HSP25 expression, but inhibited GI-GPx expression in the epithelium of distal colon. RS3 increased the number of predominantly acidic mucin containing goblet cells in the distal colon, but had no effect on the goblet cell count. We conclude that hydrothermally treated RS3 prevented colon carcinogenesis, and that this effect was mediated by enhanced apoptosis of damaged cells accompanied by changes in parameters of dedifferentiation in colonic mucosa.
CitationCarcinogenesis 2006, 27 (9):1849-1859
DescriptionDietary modulation of cancer & cancer biomarkers Dietary item or component studied:butyrate in resistant starch 3 (RS3)Outcome studied (cancer or cancer biomarker):actual cancer cancerStudy type(in vitro, animals, humans):Male Sprague-Dawley ratsTissue/biological material/sample size:The first 0.5 cm of the proximal colon and the final 0.5 cm of the distal colonMode of exposure (if in vivo):s.c. injection(for1,2-dimethylhydrazine (DMH)) and oral( for RS3diet)Impact on outcome (including dose-response):Six of eleven animals developed adenocarcinoma and one as adenoma located in the late proximal and earlydistal large intestine (1 tumor after 30%, 1 after 40%, 1 after 50%, 3 after 60% and 1 after 70% of the length of the large intestine).Quality control:Immunohistochemistry and TUNEL assay was used For the detection of Ki-67, active caspase-3, PKC-d, HSP25 and GI-GPxDietary modulation of carcinogenesis-related pathwaysDietary item or component studied:butyrate in resistant starch3 (RS3)Pathways studied: butyrate-producing resistant starch in the development of colorectal neoplasiaStudy type (in vitro, animals, humans):Male Sprague-Dawley ratsTissue/biological material/sample size:The first 0.5 cm of the proximal colon and the final 0.5 cm of the distal colonMode of exposure (if in vivo):s.c. injection(for1,2-dimethylhydrazine (DMH)) and oral( for RS3diet)Impact on pathway (including dose-response):all increased in the diet treaded mice, cytosolic GI-GPx of the distal colon was decreased and didnt affect the goblet cell count. Keywords classification: 1,2-Dimethylhydrazine;Animals;Apoptosis;chemically induced;Carcinogens;Cell Differentiation;Cell Proliferation;Colonic Neoplasms;dietary modulation of cancer & cancer biomarkers;dietary modulation of carcinogenesis-related pathways;Dietary Carbohydrates;Food;Germany;Glutathione;Glutathione Peroxidase;humans;Heat-Shock Proteins;metabolism;Male;Neoplasm Proteins;pathology;pharmacology;Peroxidase;Protein Kinase C-delta;Proteins;Rats;Rats,Sprague-Dawley;Research;Starch;