Grape antioxidant dietary fiber inhibits intestinal polyposis in Apc(Min/) mice: relation to cell cycle and immune response
Por:
S. SANCHEZ-TENA, D. LIZARRAGA, A. MIRANDA, M. VINARDELL, F. GARCIA-GARCIA, J. DOPAZO, J. TORRES, F. SAURA-CALIXTO, G. CAPELLA and M. CASCANTE
Publicada:
1 ago 2013
Resumen:
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%), 12mm (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 G(1) 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.
Filiaciones:
S. SANCHEZ-TENA:
Univ Barcelona, Fac Biol, Dept Biochem & Mol Biol, IBUB, E-08028 Barcelona, Spain
CSIC, Unit Associated, E-08028 Barcelona, Spain
IDIBAPS, Barcelona 08036, Spain
D. LIZARRAGA:
Maastricht Univ, Dept Hlth Risk Anal & Toxicol, NL-6200 Maastricht, Netherlands
A. MIRANDA:
Univ Barcelona, Fac Biol, Dept Biochem & Mol Biol, IBUB, E-08028 Barcelona, Spain
CSIC, Unit Associated, E-08028 Barcelona, Spain
IDIBAPS, Barcelona 08036, Spain
M. VINARDELL:
Univ Barcelona, Fac Farm, Dept Fisiol, E-08028 Barcelona, Spain
:
Funct Genom Node, Natl Inst Bioinformat, E-46013 Valencia, Spain
Ctr Invest Principe Felipe, Dept Bioinformat, E-46013 Valencia, Spain
CIBER Enfermedades Raras CIBERER, E-46013 Valencia, Spain
:
Funct Genom Node, Natl Inst Bioinformat, E-46013 Valencia, Spain
Ctr Invest Principe Felipe, Dept Bioinformat, E-46013 Valencia, Spain
CIBER Enfermedades Raras CIBERER, E-46013 Valencia, Spain
J. TORRES:
Inst Adv Chem Catalonia IQAC CSIC, Barcelona 08034, Spain
F. SAURA-CALIXTO:
Inst Food Sci & Technol & Nutr ICTAN CSIC, Dept Metab & Nutr, Madrid 28040, Spain
G. CAPELLA:
IDIBELL Catalan Inst Oncol, Translat Res Lab, E-08908 Lhospitalet De Llobregat, Spain
M. CASCANTE:
Univ Barcelona, Fac Biol, Dept Biochem & Mol Biol, IBUB, E-08028 Barcelona, Spain
CSIC, Unit Associated, E-08028 Barcelona, Spain
IDIBAPS, Barcelona 08036, Spain
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