| The cannabinoid CB1 receptor antagonist rimonabant (SR141716) inhibits human breast cancer cell proliferation through a lipid raft-mediated mechanism. | |
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MedLine Citation:
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PMID: 16822929 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The endocannabinoid system has been shown to modulate key cell-signaling pathways involved in cancer cell growth. In this study, we show that cannabinoid receptor type 1 (CB1) antagonist Rimonabant (SR141716) inhibited human breast cancer cell proliferation, being more effective in highly invasive metastatic MDA-MB-231 cells than in less-invasive T47D and MCF-7 cells. The SR141716 antiproliferative effect was not accompanied by apoptosis or necrosis and was characterized by a G1/S-phase cell cycle arrest, decreased expression of cyclin D and E, and increased levels of cyclin-dependent kinase inhibitor p27KIP1. We have also shown that SR141716 exerted a significant antiproliferative action, in vivo, by reducing the volume of xenograft tumors induced by MDA-MB-231 injection in mice. On the other hand, at the concentration range in which we observed the antiproliferative effect in tumor cells, we did not observe evidence of any genotoxic effect on normal cells. Our data also indicate that the SR141716 antiproliferative effect requires lipid raft/caveolae integrity to occur. Indeed, we found that CB1 receptor (CB1R) is completely displaced from lipid rafts in SR141716-treated MDA-MB-231 cells, and cholesterol depletion by methyl-beta-cyclodextrin strongly prevented SR141716-mediated antiproliferative effect. Taken together, our results suggest that SR141716 inhibits human breast cancer cell growth via a CB1R lipid raft/caveolae-mediated mechanism. |
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Authors:
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Daniela Sarnataro; Simona Pisanti; Antonietta Santoro; Patrizia Gazzerro; Anna Maria Malfitano; Chiara Laezza; Maurizio Bifulco |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2006-07-05 |
Journal Detail:
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Title: Molecular pharmacology Volume: 70 ISSN: 0026-895X ISO Abbreviation: Mol. Pharmacol. Publication Date: 2006 Oct |
Date Detail:
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Created Date: 2006-09-25 Completed Date: 2006-11-29 Revised Date: 2007-10-17 |
Medline Journal Info:
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Nlm Unique ID: 0035623 Medline TA: Mol Pharmacol Country: United States |
Other Details:
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Languages: eng Pagination: 1298-306 Citation Subset: IM |
Affiliation:
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Dipartimento di Scienze Farmaceutiche, Università degli Studi di Salerno, Via Ponte don Melillo, 84084 Fisciano (Salerno), Italy. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Breast Neoplasms / metabolism*, pathology* CHO Cells Caveolae / metabolism* Cell Cycle Cell Line, Tumor Cell Proliferation / drug effects* Cricetinae Cricetulus Female Humans MAP Kinase Signaling System Membrane Microdomains / metabolism* Mice Piperidines / pharmacology* Pyrazoles / pharmacology* Receptor, Cannabinoid, CB1 / antagonists & inhibitors*, physiology Transplantation, Heterologous / pathology* Tumor Burden |
| Chemical | |
Reg. No./Substance:
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0/Piperidines; 0/Pyrazoles; 0/Receptor, Cannabinoid, CB1; 158681-13-1/rimonabant |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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