Document Detail


The cannabinoid CB1 receptor antagonist rimonabant (SR141716) inhibits human breast cancer cell proliferation through a lipid raft-mediated mechanism.
MedLine Citation:
PMID:  16822929     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Daniela Sarnataro; Simona Pisanti; Antonietta Santoro; Patrizia Gazzerro; Anna Maria Malfitano; Chiara Laezza; Maurizio Bifulco
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-07-05
Journal Detail:
Title:  Molecular pharmacology     Volume:  70     ISSN:  0026-895X     ISO Abbreviation:  Mol. Pharmacol.     Publication Date:  2006 Oct 
Date Detail:
Created Date:  2006-09-25     Completed Date:  2006-11-29     Revised Date:  2007-10-17    
Medline Journal Info:
Nlm Unique ID:  0035623     Medline TA:  Mol Pharmacol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1298-306     Citation Subset:  IM    
Affiliation:
Dipartimento di Scienze Farmaceutiche, Università degli Studi di Salerno, Via Ponte don Melillo, 84084 Fisciano (Salerno), Italy.
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MeSH Terms
Descriptor/Qualifier:
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:
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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