title: Revisiting CB1 receptor as drug target in human melanoma.
abstract: Previous studies have indicated the antitumoral effect of human melanocytes, human melanoma cell lines expressing CB1 receptor (CB1), and of the peritumoral administration of endocannabinoids. In the present study, we systematically screened several human melanoma cell lines for the expression of CNR1 and demonstrated transcription of the authentic gene. The product of CNR1, the CB1 protein, was found localized to the cell membrane as well as to the cytoskeleton. Further, the studied human melanoma cell lines expressed functional CB1 since physiological and synthetic ligands, anandamide (AEA), Met-F-AEA, ACEA and AM251 showed a wide range of biological effects in vitro, for example anti-proliferative, proapoptotic and anti-migratory. More importantly, our studies revealed that systemic administration of a stable CB1 agonist, ACEA, into SCID mice specifically inhibited liver colonization of human melanoma cells. Since therapeutic options for melanoma patients are still very limited, the endocannabinoid-CB1 receptor system may offer a novel target.
authors.affiliation: 2nd Department of Pathology, Semmelweis University, Üllői út 93., Budapest, 1091, Hungary. steveken12@yahoo.com
authors.forename: István
authors.initials: I
authors.lastname: Kenessey
authors.forename: Balázs
authors.initials: B
authors.lastname: Bánki
authors.forename: Agnes
authors.initials: A
authors.lastname: Márk
authors.forename: Norbert
authors.initials: N
authors.lastname: Varga
authors.forename: József
authors.initials: J
authors.lastname: Tóvári
authors.forename: Andrea
authors.initials: A
authors.lastname: Ladányi
authors.forename: Erzsébet
authors.initials: E
authors.lastname: Rásó
authors.forename: József
authors.initials: J
authors.lastname: Tímár
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001095:Arachidonic Acids / Q000494:pharmacology; D001483:Base Sequence; D002186:Cannabinoids / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D016503:Drug Delivery Systems / Q000379:methods*; D063388:Endocannabinoids / Q000494:pharmacology; D006801:Humans; D008024:Ligands; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000556:secondary; D008545:Melanoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D016513:Mice, SCID; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D010880:Piperidines / Q000494:pharmacology; D053284:Polyunsaturated Alkamides / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: C443759:2-methylarachidonyl-2'-fluoroethylamide; D001095:Arachidonic Acids; D002186:Cannabinoids; D063388:Endocannabinoids; D008024:Ligands; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; C119325:arachidonyl-2-chloroethylamide; C103505:AM 251; C078814:anandamide