Grape antioxidant dietary fiber inhibits intestinal polyposis in ApcMin/+ mice: relation to cell cycle and immune response.

TitleGrape antioxidant dietary fiber inhibits intestinal polyposis in ApcMin/+ mice: relation to cell cycle and immune response.
Publication TypeJournal Article
Year of Publication2013
AuthorsSánchez-Tena, S, Lizarraga, D, Miranda, A, Vinardell, MP, Garcia-Garcia, F, Dopazo, J, Torres, JL, Saura-Calixto, F, Capellà, G, Cascante, M
JournalCarcinogenesis
Volume34
Issue8
Pagination1881-8
Date Published2013 Aug
ISSN1460-2180
KeywordsAnimals; Antioxidants; Body Weight; Carcinogenesis; Cell Cycle; Cell Cycle Checkpoints; Colorectal Neoplasms; Dietary Fiber; Dietary Supplements; Down-Regulation; G1 Phase; Inflammation; Intestinal Polyposis; Intestinal Polyps; Intestine, Small; Male; Mice; Transcriptome; Vitis
Abstract

Epidemiological and experimental studies suggest that fiber and phenolic compounds might have a protective effect on the development of colon cancer in humans. Accordingly, we assessed the chemopreventive efficacy and associated mechanisms of action of a lyophilized red grape pomace containing proanthocyanidin (PA)-rich dietary fiber [grape antioxidant dietary fiber (GADF)] on spontaneous intestinal tumorigenesis in the Apc(Min/+) mouse model. Mice were fed a standard diet (control group) or a 1% (w/w) GADF-supplemented diet (GADF group) for 6 weeks. GADF supplementation greatly reduced intestinal tumorigenesis, significantly decreasing the total number of polyps by 76%. Moreover, size distribution analysis showed a considerable reduction in all polyp size categories [diameter <1mm (65%), 1-2mm (67%) and >2mm (87%)]. In terms of polyp formation in the proximal, middle and distal portions of the small intestine, a decrease of 76, 81 and 73% was observed, respectively. Putative molecular mechanisms underlying the inhibition of intestinal tumorigenesis were investigated by comparison of microarray expression profiles of GADF-treated and non-treated mice. We observed that the effects of GADF are mainly associated with the induction of a G1 cell cycle arrest and the downregulation of genes related to the immune response and inflammation. Our findings show for the first time the efficacy and associated mechanisms of action of GADF against intestinal tumorigenesis in Apc(Min/+) mice, suggesting its potential for the prevention of colorectal cancer.

DOI10.1093/carcin/bgt140
PubMed ID23615403