Cannabinoid receptor ligands as potential anticancer agents - high hopes for new therapies?

Objectives The endocannabinoid system is all endogenous lipid signalling network comprising arachidonic-acid-derived ligands, cannabinoid (CB) receptors, transporters and endocannabinoid degrading enzymes. The CB1 receptor is predominantly expressed in neurons but is also co-expressed with the CB2 receptor in peripheral tissues. In recent years, CB receptor ligands. including Delta(9)-tetrahydrocannabinol. have been proposed as potential anticancer agents. Key findings This review critically discusses the pharmacology of CB receptor activation as a novel therapeutic anticancer strategy in terms of ligand selectivity. tissue specificity and potency. Intriguingly, antitumor effects mediated by cannabinoids are not confined to inhibition of cancer cell proliferation, cannabinoids also reduce angiogenesis, cell migration and metastasis, inhibit carcinogenesis and attenuate inflammatory processes. In the last decade several new selective CB1 and CB2 receptor agents have been described. but most Studies in the area of cancer research have used non-selective CB ligands. Moreover, many of these ligands exert prominent CB receptor-independent pharmacological effects, Such as activation of the G-protein-coupled receptor GPR55, peroxisome proliferator-activated receptor gamma and the transient receptor potential vanilloid channels. Summary The role of the endocannabinoid system in tumourigenesis is still poorly understood and the molecular mechanisms of cannabinoid anticancer action need to be elucidated. The development of CB2-selective anticancer agents could be advantageous ill light of the unwanted central effects exerted by CB1 receptor ligands. Probably the most interesting question is whether cannabinoids Could be useful ill chemoprevention or in combination with established chemotherapeutic agents.