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%), 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.
Asunto(s)
Antioxidantes/farmacología , Ciclo Celular/efectos de los fármacos , Fibras de la Dieta/farmacología , Poliposis Intestinal/tratamiento farmacológico , Poliposis Intestinal/inmunología , Vitis/química , Animales , Peso Corporal/efectos de los fármacos , Peso Corporal/genética , Peso Corporal/inmunología , Carcinogénesis/efectos de los fármacos , Carcinogénesis/genética , Carcinogénesis/inmunología , Ciclo Celular/genética , Ciclo Celular/inmunología , Puntos de Control del Ciclo Celular/efectos de los fármacos , Puntos de Control del Ciclo Celular/genética , Puntos de Control del Ciclo Celular/inmunología , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/inmunología , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/prevención & control , Suplementos Dietéticos , Regulación hacia Abajo/efectos de los fármacos , Regulación hacia Abajo/inmunología , Fase G1/efectos de los fármacos , Fase G1/genética , Fase G1/inmunología , Inflamación/tratamiento farmacológico , Inflamación/genética , Inflamación/inmunología , Inflamación/metabolismo , Poliposis Intestinal/genética , Poliposis Intestinal/metabolismo , Pólipos Intestinales/tratamiento farmacológico , Pólipos Intestinales/genética , Pólipos Intestinales/inmunología , Pólipos Intestinales/metabolismo , Intestino Delgado/efectos de los fármacos , Intestino Delgado/inmunología , Intestino Delgado/metabolismo , Masculino , Ratones , Transcriptoma/efectos de los fármacos , Transcriptoma/inmunologíaRESUMEN
Bidens pilosa is an annual plant from tropical America with anti-inflammatory properties, laryngitis, headache and digestive disorders, among others. Its wide pharmacological applications can be attributed to its chemical composition, with inhibitory effects on pathogenic microorganisms and flavonoids, wich show strong antioxidant capacities. We investigated the antioxidant activity of an aqueous infusion of Bidens pilosa by studying its protective effect on the hemolysis by an initiator of radicals such as 2,2-azobis (2-amidinopropane) dihydrochloride (AAPH)(AU)