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

Abstract

The bitter acids of hops (Humulus lupulus L.) mainly consist of humulones or alpha-acids and lupulones or beta-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 microg/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.

• Authors: Virginie Lamy, Stamatiki Roussi, Mehdi Chaabi, Francine Gossé, Nicolas Schall, Annelise Lobstein, Francis Raul
• Journal: Carcinogenesis (Carcinogenesis) Vol. 28 Issue 7 Pg. 1575-81 (Jul 2007) ISSN: 0143-3334 [Print] England
• PMID: 17434926 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anticarcinogenic Agents
• Fas Ligand Protein
• Plant Preparations
• Receptors, TNF-Related Apoptosis-Inducing Ligand
• Terpenes
• fas Receptor
• lupulon
• Azoxymethane

Topics

• Animals
• Anticarcinogenic Agents (pharmacology, therapeutic use)
• Apoptosis (drug effects)
• Azoxymethane
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Colonic Neoplasms (chemically induced, pathology, prevention & control)
• Disease Models, Animal
• Fas Ligand Protein (metabolism)
• Humans
• Intestinal Mucosa (metabolism, pathology)
• Male
• Mitochondrial Membranes (drug effects, physiology)
• Neoplasm Metastasis
• Permeability
• Plant Preparations (chemistry)
• Rats
• Rats, Wistar
• Receptors, TNF-Related Apoptosis-Inducing Ligand (metabolism)
• Terpenes (pharmacology, therapeutic use)
• fas Receptor (metabolism)