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Journal of Environmental Pathology, Toxicology and Oncology
IF: 1.15 5-Year IF: 1.4 SJR: 0.519 SNIP: 0.613 CiteScore™: 1.61

ISSN Print: 0731-8898
ISSN Online: 2162-6537

Journal of Environmental Pathology, Toxicology and Oncology

DOI: 10.1615/JEnvironPatholToxicolOncol.2013005859
pages 377-387

Role of Cannabinoid and Vanilloid Receptors in Invasion of Human Breast Carcinoma Cells

N. Farsandaj
Department of Toxicology and Pharmacology, Faculty of Pharmacy, and Poisoning Research Center, Tehran University of Medical Sciences, Tehran, Iran
Mohammad Hossein Ghahremani
Departments of Toxicology and Pharmacology, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; Department of Molecular Medicine, School of Advance Medical Technologies, Tehran University of Medical Sciences, Tehran, Iran
Seyed Nasser Ostad
Department of Toxicology and Pharmacology, Faculty of Pharmacy, and Poisoning Research Center, Tehran University of Medical Sciences, Tehran, Iran

ABSTRACT

It is known that the diversified effects of cannabinoid on the fate of carcinoma cells are mediated predominantly through receptors. However, little is known about the effects of the individual activities of cannabinoid and noncannabinoid receptors. Here we investigate the role of cannabinoid receptor (CB) 1, CB2, and transient receptor potential vanilloid type 1 in cell proliferation and invasion patterns in the MDA-MB-231 cell line.
Our results showed that activation of CB1 and vanilloid receptors by methanandamide, a nonselective agonist, and arachidonyl-2'-choloroethylamide (ACEA) and N-oleoyldopamine, selective agonists, reduced invasion of MDA-MB-231 cells at pharmacological concentrations. Accordingly, CB1 activation resulted in decreased expression of matrix metalloproteinase (MMP) 2. On the other hand, administration of a CB2 agonist (CB65) increased cell invasion and expression of MMP2. The data obtained from MTT assay did not show any correlation between reduced invasion and cytotoxic effects of drugs. In addition, the level of vascular endothelial growth factor was significantly reduced in treatment with (R)-(+)-methanandamide, ACEA, CB65, and AM251 (a potent agonist for GPR55 and selective antagonist of CB1) compared with control. Elevated expression of cyclooxygenase-2 was observed in all of the MDA-MB-231 cells treated with agonists.
These results underline the influence of cannabinoid and vanilloid receptors on the invasiveness of MDA-MB-231 human breast carcinoma cells.