RT Journal Article
SR Electronic
T1 Inhibition of Rat C6 Glioma Cell Proliferation by Endogenous and Synthetic Cannabinoids. Relative Involvement of Cannabinoid and Vanilloid Receptors
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 951
OP 959
VO 299
IS 3
A1 Jacobsson, Stig O. P.
A1 Wallin, Thomas
A1 Fowler, Christopher J.
YR 2001
UL http://jpet.aspetjournals.org/content/299/3/951.abstract
AB 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 byl-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. The American Society for Pharmacology and Experimental Therapeutics