title: Grape antioxidant dietary fiber inhibits intestinal polyposis in ApcMin/+ mice: relation to cell cycle and immune response.
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.
authors.affiliation: Department of Biochemistry and Molecular Biology, IBUB, Faculty of Biology, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Susana
authors.initials: S
authors.lastname: Sánchez-Tena
authors.forename: Daneida
authors.initials: D
authors.lastname: Lizárraga
authors.forename: Anibal
authors.initials: A
authors.lastname: Miranda
authors.forename: Maria P
authors.initials: MP
authors.lastname: Vinardell
authors.forename: Francisco
authors.initials: F
authors.lastname: García-García
authors.forename: Joaquín
authors.initials: J
authors.lastname: Dopazo
authors.forename: Josep L
authors.initials: JL
authors.lastname: Torres
authors.forename: Fulgencio
authors.initials: F
authors.lastname: Saura-Calixto
authors.forename: Gabriel
authors.initials: G
authors.lastname: Capellà
authors.forename: Marta
authors.initials: M
authors.lastname: Cascante
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D063646:Carcinogenesis / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D002453:Cell Cycle / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D059447:Cell Cycle Checkpoints / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D015179:Colorectal Neoplasms / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control; D004043:Dietary Fiber / Q000494:pharmacology*; D019587:Dietary Supplements; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology; D016193:G1 Phase / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D007249:Inflammation / Q000188:drug therapy / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D044483:Intestinal Polyposis / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D007417:Intestinal Polyps / Q000188:drug therapy / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007421:Intestine, Small / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D059467:Transcriptome / Q000187:drug effects / Q000276:immunology; D027843:Vitis / Q000737:chemistry*
chemical_list: D000975:Antioxidants; D004043:Dietary Fiber