Department of Pharmacology and Toxicology, University of Otago, Dunedin, New Zealand.
Cancer Manag Res. 2013 Aug 30;5:301-13. doi: 10.2147/CMAR.S36105. eCollection 2013.
Cannabinoids have been attracting a great deal of interest as potential anticancer agents. Originally derived from the plant Cannabis sativa, there are now a number of endo-, phyto- and synthetic cannabinoids available. This review summarizes the key literature to date around the actions, antitumor activity, and mechanisms of action for this broad range of compounds. Cannabinoids are largely defined by an ability to activate the cannabinoid receptors - CB1 or CB2. The action of the cannabinoids is very dependent on the exact ligand tested, the dose, and the duration of exposure. Some cannabinoids, synthetic or plant-derived, show potential as therapeutic agents, and evidence across a range of cancers and evidence in vitro and in vivo is starting to be accumulated. Studies have now been conducted in a wide range of cell lines, including glioma, breast, prostate, endothelial, liver, and lung. This work is complemented by an increasing body of evidence from in vivo models. However, many of these results remain contradictory, an issue that is not currently able to be resolved through current knowledge of mechanisms of action. While there is a developing understanding of potential mechanisms of action, with the extracellular signal-regulated kinase pathway emerging as a critical signaling juncture in combination with an important role for ceramide and lipid signaling, the relative importance of each pathway is yet to be determined. The interplay between the intracellular pathways of autophagy versus apoptosis is a recent development that is discussed. Overall, there is still a great deal of conflicting evidence around the future utility of the cannabinoids, natural or synthetic, as therapeutic agents.
大麻素作为潜在的抗癌药物引起了极大的关注。它们最初来源于大麻植物 Cannabis sativa，现在有许多内源性、植物源性和合成大麻素可供使用。这篇综述总结了迄今为止关于这一大类化合物的作用、抗肿瘤活性和作用机制的关键文献。大麻素的主要特征是能够激活大麻素受体 - CB1 或 CB2。大麻素的作用非常依赖于测试的确切配体、剂量和暴露时间。一些大麻素，无论是合成的还是植物源性的，都显示出作为治疗剂的潜力，并且在各种癌症中的体外和体内证据开始积累。目前已经在广泛的细胞系中进行了研究，包括神经胶质瘤、乳腺癌、前列腺癌、内皮细胞、肝脏和肺癌。这方面的工作得到了越来越多的体内模型证据的补充。然而，许多这些结果仍然存在矛盾，这是一个目前无法通过对作用机制的现有知识来解决的问题。虽然对于潜在的作用机制有了一定的认识，细胞外信号调节激酶途径作为一个关键的信号交汇点，与神经酰胺和脂质信号的重要作用相结合，但每个途径的相对重要性尚未确定。自噬与细胞凋亡的细胞内途径之间的相互作用是一个新的发展，本文对此进行了讨论。总的来说，关于天然或合成大麻素作为治疗剂的未来用途，仍然存在大量相互矛盾的证据。
