a Institute of Pharmacology and Toxicology , Rostock University Medical Center , Rostock , Germany.
Drug Metab Rev. 2018 Feb;50(1):26-53. doi: 10.1080/03602532.2018.1428344. Epub 2018 Feb 1.
The endocannabinoid system is currently under intense investigation due to the therapeutic potential of cannabinoid-based drugs as treatment options for a broad variety of diseases including cancer. Besides the canonical endocannabinoid system that includes the cannabinoid receptors CB and CB and the endocannabinoids N-arachidonoylethanolamine (anandamide) and 2-arachidonoylglycerol, recent investigations suggest that other fatty acid derivatives, receptors, enzymes, and lipid transporters likewise orchestrate this system as components of the endocannabinoid system when defined as an extended signaling network. As such, fatty acids acting at cannabinoid receptors (e.g. 2-arachidonoyl glyceryl ether [noladin ether], N-arachidonoyldopamine) as well as endocannabinoid-like substances that do not elicit cannabinoid receptor activation (e.g. N-palmitoylethanolamine, N-oleoylethanolamine) have raised interest as anticancerogenic substances. Furthermore, the endocannabinoid-degrading enzymes fatty acid amide hydrolase and monoacylglycerol lipase, lipid transport proteins of the fatty acid binding protein family, additional cannabinoid-activated G protein-coupled receptors, members of the transient receptor potential family as well as peroxisome proliferator-activated receptors have been considered as targets of antitumoral cannabinoid activity. Therefore, this review focused on the antitumorigenic effects induced upon modulation of this extended endocannabinoid network.
内源性大麻素系统目前正受到广泛研究，因为基于大麻素的药物具有治疗潜力，可作为多种疾病（包括癌症）的治疗选择。除了包括大麻素受体 CB 和 CB 和内源性大麻素 N-花生四烯酰乙醇胺（大麻素）和 2-花生四烯酰甘油在内的经典内源性大麻素系统外，最近的研究表明，其他脂肪酸衍生物、受体、酶和脂质转运蛋白也同样作为内源性大麻素系统的组成部分，作为内源性大麻素系统的扩展信号网络。因此，作用于大麻素受体的脂肪酸（例如 2-花生四烯酰甘油醚 [大麻素醚]、N-花生四烯酰多巴胺）以及不会引发大麻素受体激活的内源性大麻素样物质（例如 N-棕榈酰乙醇胺、N-油酰乙醇胺）已作为抗癌物质引起了关注。此外，内源性大麻素降解酶脂肪酸酰胺水解酶和单酰甘油脂肪酶、脂肪酸结合蛋白家族的脂质转运蛋白、其他大麻素激活的 G 蛋白偶联受体、瞬时受体电位家族的成员以及过氧化物酶体增殖物激活受体也被认为是抗肿瘤大麻素活性的靶点。因此，本综述重点关注了通过调节这个扩展的内源性大麻素网络所诱导的抗肿瘤作用。
