Department of Drug Dependence Research, National Institute of Mental Health, National Center of Neurology and Psychiatry, Japan.
Toxicol Lett. 2011 Nov 10;207(1):12-7. doi: 10.1016/j.toxlet.2011.08.021. Epub 2011 Sep 2.
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.
已报道称，含有与Δ⁹-四氢大麻酚具有相似药理活性的合成大麻素的“香料”在全球范围内分布。在本研究中，我们评估了合成大麻素 CP-55,940、CP-47,497 和 CP-47,497-C8 对 NG 108-15 细胞的细胞毒性，并研究了它们的细胞毒性机制。CP-55,940、CP-47,497 和 CP-47,497-C8 均以浓度依赖的方式对 NG 108-15 细胞具有细胞毒性。这些合成大麻素的细胞毒性可通过与选择性 CB₁ 受体拮抗剂 AM251 预孵育而被抑制，但不能被选择性 CB₂ 受体拮抗剂 AM630 抑制。用半胱天冬酶-3 抑制剂预孵育可显著抑制这些合成大麻素对 NG 108-15 细胞的细胞毒性。用这些大麻素对细胞进行 Annexin V 染色也证实了细胞凋亡的诱导。我们的结果表明，合成大麻素对 NG 108-15 细胞的细胞毒性是由 CB₁ 受体介导的，而不是由 CB₂ 受体介导的，进一步表明半胱天冬酶级联反应可能在这些合成大麻素诱导的细胞凋亡中发挥重要作用。
