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Cytotoxicity of synthetic cannabinoids found in "Spice" products: the role of cannabinoid receptors and the caspase cascade in the NG 108-15 cell line.
- Source :
-
Toxicology letters [Toxicol Lett] 2011 Nov 10; Vol. 207 (1), pp. 12-7. Date of Electronic Publication: 2011 Sep 02. - Publication Year :
- 2011
-
Abstract
- The worldwide distribution of "Spice" that contains synthetic cannabinoids with a pharmacological activity similar to Δ⁹-tetrahydrocannabinol has been reported. In the current study, we evaluated the cytotoxicity of the synthetic cannabinoids, CP-55,940, CP-47,497 and CP-47,497-C8 towards NG 108-15 cells and investigated their mechanism of cytotoxicity. CP-55,940, CP-47,497 and CP-47,497-C8 were all cytotoxic for NG 108-15 cells in a concentration-dependent manner. The cytotoxicity of these synthetic cannabinoids was suppressed by preincubation with the selective CB₁ receptor antagonist AM251, but not with the selective CB₂ receptor antagonist AM630. Preincubation with a caspase-3 inhibitor significantly suppressed the cytotoxicity of these synthetic cannabinoids for NG 108-15 cells. Induction of apoptosis by these cannabinoids was also confirmed by staining of the cells with annexin V. Our results indicate that the cytotoxicity of synthetic cannabinoids towards NG 108-15 cells is mediated by the CB₁ receptor, but not by the CB₂ receptor, and further suggest that caspase-cascades may play an important role in the apoptosis induced by these synthetic cannabinoids.<br /> (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)
- Subjects :
- Cannabinoids antagonists & inhibitors
Caspase Inhibitors
Cell Line, Tumor
Cell Survival drug effects
Cyclohexanols antagonists & inhibitors
Cysteine Proteinase Inhibitors pharmacology
Drug Interactions
Humans
Indoles pharmacology
Microscopy, Fluorescence
Oligopeptides pharmacology
Piperidines pharmacology
Pyrazoles pharmacology
Apoptosis physiology
Cannabinoids toxicity
Caspase 3 metabolism
Cyclohexanols toxicity
Receptor, Cannabinoid, CB1 metabolism
Receptor, Cannabinoid, CB2 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1879-3169
- Volume :
- 207
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Toxicology letters
- Publication Type :
- Academic Journal
- Accession number :
- 21907772
- Full Text :
- https://doi.org/10.1016/j.toxlet.2011.08.021