Carcinogenesis Advance Access published online on March 24, 2005
Carcinogenesis, doi:10.1093/carcin/bgi074
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1 Laboratoire d'Oncologie Nutritionnelle, Université Louis Pasteur EA 3430, Institut de Recherche contre les Cancers de l'Appareil Digestif (IRCAD), Strasbourg, France
* To whom correspondence should be addressed. Apples contain several classes of polyphenols: monomers (catechins, epicatechins) and oligomers / polymers, such as the procyanidins. Our aim was 1) to study anti-proliferative mechanisms on human metastatic colon carcinoma (SW620 cells) of apple polyphenol fractions (monomers or procyanidins) and 2) to evaluate their anti-carcinogenic properties in vivo. Two polyphenol-enriched fractions were isolated from apples. Fraction NP contained 73% phenolic monomers and no procyanidins. Fraction P contained 78% procyanidins and no monomers. Inhibition of SW620 cell growth was only observed with fraction P (IC50 = 45 µg/ml). After 24 h exposure of cells to fraction P protein kinase C activity was inhibited by 70% and a significant increase in ERK1,2 and JNK 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 during two 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 to 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.
Received January 18, 2005
Revised March 10, 2005
Accepted March 12, 2005
MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION
Chemopreventive properties of apple procyanidins on human colon cancer-derived metastatic SW620 cells and in a rat model of colon carcinogenesis
2 Unité de Recherches Cidricoles, Institut National de Recherche Agronomique (INRA), Biotransformation des Fruits et Légumes, Le Rheu, France
3 Laboratoire de Pharmacognosie, Université Louis Pasteur, Faculté de Pharmacie, Illkirch, France
Francis Raul, E-mail: francis.raul{at}ircad.u-strasbg.fr
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