Dietary resistant starch type 3 prevents tumor induction by 1,2-dimethylhydrazine and alters proliferation, apoptosis and dedifferentiation in rat colon

Abstract

Some 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.

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

“…31 Few in vivo studies examining tumorigenesis with intervention by RS or other fermentable substrates have investigated the colonic apoptotic response at this late time point. Bauer-Marinovic et al 8 however did observe a significant increase in apoptosis in rats fed hydrothermally treated RS 3 . In this particular study apoptosis was measured in the colon of rats that had received an intensive and prolonged carcinogen schedule, namely 20 s.c. injections of DMH where the rats were killed one week after the last DMH injection.…”

“…These are summarised in Young et al 4 and the results are conflicting. More recently hydrothermally treated RS 3 protected against dimethylhydrazine (DMH)-induced colon carcinogenesis 8 and high amylose maize starch protected against AOM-induced colon cancer. 9 There are several explanations for the varying results between the reported studies: the different carcinogen protocols (dose and duration), differences in starch type, feeding regimens, lack of effect on fermentation parameters and the comparative control diet.…”

Is resistant starch protective against colorectal cancer via modulation of the WNT signalling pathway?

“…This includes the study by Wacker et al (64) which administered the largest dose of RS (up to 59·7 g /d). In contrast, a number of studies have reported reduced cell proliferation in the colorectum of individuals with neoplasia (25,26) . Importantly, we have also shown that supplementation of CRC patients with a 1:1 blend of Novelose 240 and Novelose 330 (RS types 2 and 3) reduced the proportion of mitotic cells in the top half of the crypt (65) .…”

“…While some studies have indicated a chemoprotective effect of RS, others have reported no effect and some have observed adverse effects. In rats treated with 1,2-dimethylhydrazine dihydrochloride (DMH; a carcinogen used widely in experimental studies of CRC formation), incidence of tumours was reduced when the animals were fed Novelose 330 (a type 3 RS) compared with those fed a standard diet (25) . High-amylose maize starch (HAMS; a type 2 RS) has also been shown to reduce incidence and the number of adenocarcinomas in rats when the HAMS diet was provided for 4 weeks prior to injection with the carcinogen azoxymethane (26) .…”

Dietary Cooked Navy Beans and Their Fractions Attenuate Colon Carcinogenesis in Azoxymethane-InducedOb/ObMice

“…All of these components are primarily in aqueous-alcohol extracts of dry beans (37)(38)(39)(40). Resistant starches and nonstarch polysaccharides are cancer-preventive components (41)(42)(43), which are primarily insoluble residues from aqueous-alcohol extracts of dry beans. Cancer-preventive components in dry beans could act either alone or in combination.…”