Integrative Medicine > Cannabinoids

Abstract

Inhibition of Rat C6 Glioma Cell Proliferation by Endogenous and Synthetic Cannabinoids. Relative Involvement of Cannabinoid and Vanilloid Receptors

Stig O. P. Jacobsson , Thomas Wallin and Christopher J. Fowler 

Departments of Pharmacology and Clinical Neuroscience (S.O.P.J., T.W., C.J.F.) and Odontology (S.O.P.J.), Umeå University, Umeå, Sweden. Address correspondence to: Stig Jacobsson, Ph.D., Department of Pharmacology and Clinical Neuroscience, Umeå University, SE-901 87 Umeå, Sweden. E-mail: stig.jacobsson@pharm.umu.se

The effects of the endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG) upon rat C6 glioma cell proliferation were examined and compared with a series of synthetic cannabinoids and related compounds. 
Cells were treated with the compounds each day and cell proliferation was monitored for up to 5 days of exposure.  
AEA time- and concentration-dependently inhibited C6 cell proliferation.  
After 4 days of treatment, AEA and 2-AG inhibited C6 cell proliferation with similar potencies (IC₅₀ values of 1.6 and 1.8 µM, respectively), whereas palmitoylethanolamide showed no significant antiproliferative effects at concentrations up to 10 µM. 
The antiproliferative effects of both AEA and 2-AG were blocked completely by a combination of antagonists at cannabinoid receptors (SR141716A and SR144528 or AM251 and AM630) and vanilloid receptors (capsazepine) as well as by α-tocopherol (0.1 and 10 µM), and reduced by calpeptin (10 µM) and fumonisin B₁ (10 µM), but not by L-cycloserine (1 and 100 µM). 
CP 55,940, JW015, olvanil, and arachidonoyl-serotonin were all found to affect C6 glioma cell proliferation (IC₅₀ values of 5.6, 3.2, 5.5, and 1.6 µM, respectively), but the inhibition could not be blocked by cannabinoid + vanilloid receptor antagonists.  
It is concluded that the antiproliferative effects of the endocannabinoids upon C6 cells are brought about by a mechanism involving combined activation of both vanilloid receptors and to a lesser extent cannabinoid receptors, and leading to oxidative stress and calpain activation. 
However, there is at present no obvious universal mechanism whereby plant-derived, synthetic, and endogenous cannabinoids affect cell viability and proliferation.