Carcinogenesis Advance Access originally published online on March 24, 2005
Carcinogenesis 2005 26(7):1291-1295; doi:10.1093/carcin/bgi074
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Carcinogenesis vol.26 no.7 © Oxford University Press 2005; all rights reserved.
Chemopreventive properties of apple procyanidins on human colon cancer-derived metastatic SW620 cells and in a rat model of colon carcinogenesis
1 Laboratoire d'Oncologie Nutritionnelle, Université Louis Pasteur EA 3430, Institut de Recherche contre les Cancers de l'Appareil Digestif (IRCAD), Strasbourg, France, 2 Unité de Recherches Cidricoles, Institut National de Recherche Agronomique (INRA), Biotransformation des Fruits et Légumes, Le Rheu, France and 3 Laboratoire de Pharmacognosie, Université Louis Pasteur, Faculté de Pharmacie, Illkirch, France
* To whom correspondence should be addressed at: Department of Nutritional Oncology, IRCAD, 1, place de l'hôpital, BP 426, 67091 Strasbourg cedex, France. Tel: +33 388119023; Fax: +33 388119097; Email: francis.raul{at}ircad.u-strasbg.fr
Apples contain several classes of polyphenols: monomers (catechins, epicatechins) and oligomers/polymers, such as the procyanidins. Our aim was (i) to study anti-proliferative mechanisms on human metastatic colon carcinoma (SW620 cells) of apple polyphenol fractions (monomers or procyanidins) and (ii) to evaluate their anti-carcinogenic properties in vivo. Two polyphenol-enriched fractions were isolated from apples. Fraction non-procyanidins contained 73% phenolic monomers and no procyanidins, while fraction procyanidins contained 78% procyanidins and no monomers. Inhibition of SW620 cell growth was only observed with fraction P (IC50 = 45 µg/ml). After a 24-h exposure of cells to fraction P, protein kinase C activity was inhibited by 70% and a significant increase in extracellular signal-regulated kinases 1 and 2 and c-jun N-terminal kinases expression was observed together with the down-regulation of polyamine biosynthesis and the activation of caspase-3. Colon carcinogenesis was induced in rats by intraperitoneal injections of azoxymethane, once a week for 2 weeks. Seven days after the last injection, Wistar rats received fraction P (0.01%) dissolved in drinking water. After 6 weeks of treatment, the colon of rats receiving procyanidins showed a significant (P < 0.01) reduction of the number of preneoplastic lesions when compared with controls receiving water. The total number of hyperproliferative crypts and of aberrant crypt foci was reduced by 50% in rats receiving 0.01% apple procyanidins in their drinking water. Our results show that apple procyanidins alter intracellular signaling pathways, polyamine biosynthesis and trigger apoptosis in tumor cells. These compounds antagonize cancer promotion in vivo. In contrast with absorbable drugs, these natural, non toxic, dietary constituents reach the colon where they are able to exert their antitumor effects.
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