title: JWH-133, a Selective Cannabinoid CB₂ Receptor Agonist, Exerts Toxic Effects on Neuroblastoma SH-SY5Y Cells.
abstract: Endocannabinoid system plays an important role in the regulation of diverse physiological functions. Although cannabinoid type 2 receptors (CB2) are involved in the modulation of immune system in peripheral tissues, recent findings demonstrated that they are also expressed in the central nervous system and could constitute a new target for the treatment of neurodegenerative disorders. At present, very little is known about the potential effects of CB2-mimetic drugs on neuronal cells. This study aimed to examine whether JWH-133, a selective CB2 receptor agonist, affects the survival of SH-SY5Y neuroblastoma cell line, a widely used experimental in vitro model to study mechanisms of toxicity and protection in nigral dopaminergic neurons. Cell viability was assessed using two complementary methods: MTT test measuring mitochondrial activity and LDHe test indicating disruption of cell membrane integrity. In addition, cell proliferation was measured using BrdU incorporation assay. JWH-133 (10-40 μM) induced a concentration-dependent decrease of SH-SY5Y cell viability and proliferation rate. Using AM-630, a reverse agonist of CB2 receptors, as well as Z-VAD-FMK, a pan-caspase inhibitor, we demonstrated that the cytotoxic effect of JWH-133 presumably was not mediated by activation of CB2 receptors or by caspase pathway. Results of this work suggest that agonists of CB2 receptors when administered in multiple/high doses may induce neuronal damage.
authors: Department of Pharmacodynamics, Medical University of Lodz, 90-151, Lodz, Muszynskiego 1, Poland.
authors: Jakub
authors: J
authors: Wojcieszak
authors: Department of Pharmacodynamics, Medical University of Lodz, 90-151, Lodz, Muszynskiego 1, Poland.
authors: Wojciech
authors: W
authors: Krzemień
authors: Department of Pharmacodynamics, Medical University of Lodz, 90-151, Lodz, Muszynskiego 1, Poland. jolanta.zawilska@umed.lodz.pl.
authors: Jolanta B
authors: JB
authors: Zawilska
mesh_terms: D063386:Cannabinoid Receptor Agonists / Q000633:toxicity*; D002186:Cannabinoids / Q000633:toxicity*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D059290:Dopaminergic Neurons / Q000187:drug effects*; D006801:Humans; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists
chemical_list: D063386:Cannabinoid Receptor Agonists; D002186:Cannabinoids; D043885:Receptor, Cannabinoid, CB2; C432747:1,1-dimethylbutyl-1-deoxy-Delta(9)-THC
keywords: Cannabinoid receptors; Cytotoxicity; JWH-133; SH-SY5Y cells