Journal Article

Chemopreventive effects of lupulone, a hop β-acid, on human colon cancer-derived metastatic SW620 cells and in a rat model of colon carcinogenesis

Virginie Lamy, Stamatiki Roussi, Mehdi Chaabi, Francine Gossé, Nicolas Schall, Annelise Lobstein and Francis Raul

in Carcinogenesis

Volume 28, issue 7, pages 1575-1581
Published in print July 2007 | ISSN: 0143-3334
Published online April 2007 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgm080
Chemopreventive effects of lupulone, a hop β-acid, on human colon cancer-derived metastatic SW620 cells and in a rat model of colon carcinogenesis

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The bitter acids of hops (Humulus lupulus L.) mainly consist of humulones or α-acids and lupulones or β-acids. We aimed to evaluate the antiproliferative mechanisms of lupulones on a human metastatic colon carcinoma-derived cell line (SW620 cells) and to assess their chemopreventive effects in a model of colon carcinogenesis. SW620 cell growth was inhibited by 70% after a 48 h exposure to lupulones (40 μg/ml). Lupulones up-regulated the expression of Fas receptor (Fas) and Fas ligand (FasL) as well as TNF-related apoptosis inducing ligand (TRAIL)-R1 (DR4) and -R2 (DR5) receptor proteins, suggesting the involvement of Fas and TRAIL receptors-mediated pathways in lupulone-induced apoptosis. Lupulones also increased the mitochondrial membrane permeability. Colon carcinogenesis was initiated in Wistar rats by intra-peritoneal injections of azoxymethane (AOM), once a week for 2 weeks. One week after the last injection, rats received lupulones (0.001 or 0.005%) in drinking water, and AOM-control rats received the excipient. After 7 months of treatment, the colon of rats receiving 0.001 and 0.005% lupulones showed, respectively, a 30 and a 50% reduction (P < 0.05) of the number of preneoplastic lesions (aberrant crypt foci). In addition, we observed a drastic reduction (70–80%) of the total number of tumors in the colon of rats treated with lupulones when compared with the AOM control group. Lupulones induced apoptosis in SW620 colon-derived metastatic cells by activating both Fas and TRAIL death receptor signaling pathways, and antagonize at a low dose (4 mg/kg/day) colon cancer development. These observations suggest the use of lupulones for colon cancer chemoprevention trials.

Journal Article.  4897 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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