title: The antimitogenic effect of the cannabinoid receptor agonist WIN55212-2 on human melanoma cells is mediated by the membrane lipid raft.
abstract: Here are reported the antiproliferative effects of the cannabinoid agonist WIN upon human melanoma cells expressing mRNA and protein for both CB1 and CB2 receptors. While WIN exerted antimitogenic effects, selective CB1 or CB2 agonists were unable to reproduce such effects and selective CB1 and CB2 antagonists did not inhibit WIN-induced cell death. Cells treated with WIN, preincubated with the lipid raft disruptor methylcyclodestrin, were rescued from death. WIN induced activation of caspases and phosphorylation of ERK that were attenuated in cultures treated with methylcyclodestrin. Membrane lipid raft complex-mediated antimitogenic effect of WIN in melanoma could represents a potential targets for a melanoma treatment.
authors.affiliation: Department of Clinical and Molecular Biomedicine, University of Catania School of Medicine, Catania, Italy.
authors.forename: Mariagrazia Rita
authors.initials: MR
authors.lastname: Scuderi
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Cantarella
authors.forename: Mimmo
authors.initials: M
authors.lastname: Scollo
authors.forename: Laurence
authors.initials: L
authors.lastname: Lempereur
authors.forename: Marco
authors.initials: M
authors.lastname: Palumbo
authors.forename: Gloria
authors.initials: G
authors.lastname: Saccani-Jotti
authors.forename: Renato
authors.initials: R
authors.lastname: Bernardini
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D048588:Benzoxazines / Q000494:pharmacology*; D002186:Cannabinoids / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival; D006801:Humans; D008545:Melanoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D021962:Membrane Microdomains / Q000187:drug effects*; D009025:Morpholines / Q000494:pharmacology*; D009281:Naphthalenes / Q000494:pharmacology*; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists* / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D048588:Benzoxazines; D002186:Cannabinoids; D009025:Morpholines; D009281:Naphthalenes; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone