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

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.