The Cannabinoid CB1 Receptor Antagonist Rimonabant (SR141716) Inhibits Human Breast Cancer Cell Proliferation through a Lipid Raft-Mediated Mechanism

• DOI: 10.1124/mol.106.025601
• Publication Date: 2006-07-06T01:04:56Z
• Authors: Daniela Sarnataro; Simona Pisanti; Antonietta Santoro; Patrizia Gazzerro; Anna Maria Malfitano; Chiara Laezza; Maurizio Bifulco
• Keywords: Rimonabant

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 proliferation, being more effective highly invasive metastatic MDA-MB-231 cells than less-invasive T47D and MCF-7 cells. SR141716 antiproliferative effect was not accompanied by apoptosis or necrosis characterized a G₁/S-phase cycle arrest, decreased expression of cyclin D E, increased levels cyclin-dependent kinase inhibitor p27^KIP1. We have also exerted significant action, vivo, reducing the volume xenograft tumors induced injection mice. On other hand, at concentration range which observed tumor cells, did observe evidence any genotoxic on normal Our data indicate requires lipid raft/caveolae integrity occur. Indeed, found CB1 (CB1R) is completely displaced from rafts SR141716-treated cholesterol depletion methyl-β-cyclodextrin strongly prevented SR141716-mediated effect. Taken together, our results suggest inhibits growth via CB1R raft/caveolae-mediated mechanism.