title: Cannabinoid receptor ligands mediate growth inhibition and cell death in mantle cell lymphoma.
abstract: We have earlier reported overexpression of the central and peripheral cannabinoid receptors CB1 and CB2 in mantle cell lymphoma (MCL), a B cell non-Hodgkin lymphoma. In this study, treatment with cannabinoid receptor ligands caused a decrease in viability of MCL cells, while control cells lacking CB1 were not affected. Interestingly, equipotent doses of the CB1 antagonist SR141716A and the CB1/CB2 agonist anandamide inflicted additive negative effects on viability. Moreover, treatment with the CB1/CB2 agonist Win-55,212-2 caused a decrease in long-term growth of MCL cells in culture. Induction of apoptosis, as measured by FACS/Annexin V-FITC, contributed to the growth suppressive effect of Win-55,212-2. Our data suggest that cannabinoid receptors may be considered as potential therapeutic targets in MCL.
authors.affiliation: Department of Laboratory Medicine, Division of Pathology, Karolinska Institutet, Karolinska University Hospital Huddinge, F-46, SE-141 86 Stockholm, Sweden.
authors.forename: Jenny
authors.initials: J
authors.lastname: Flygare
authors.forename: Kristin
authors.initials: K
authors.lastname: Gustafsson
authors.forename: Eva
authors.initials: E
authors.lastname: Kimby
authors.forename: Birger
authors.initials: B
authors.lastname: Christensson
authors.forename: Birgitta
authors.initials: B
authors.lastname: Sander
mesh_terms: D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D048588:Benzoxazines; D001706:Biopsy; D001943:Breast Neoplasms / Q000473:pathology; D063386:Cannabinoid Receptor Agonists; D063387:Cannabinoid Receptor Antagonists; D002186:Cannabinoids / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D063388:Endocannabinoids; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007952:Leukemia, Plasma Cell / Q000473:pathology; D008024:Ligands; D020522:Lymphoma, Mantle-Cell / Q000473:pathology*; D051379:Mice; D009025:Morpholines / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D053284:Polyunsaturated Alkamides; D011720:Pyrazoles / Q000494:pharmacology; D043882:Receptors, Cannabinoid / Q000145:classification / Q000378:metabolism*; D000077285:Rimonabant
chemical_list: D001095:Arachidonic Acids; D048588:Benzoxazines; D063386:Cannabinoid Receptor Agonists; D063387:Cannabinoid Receptor Antagonists; D002186:Cannabinoids; D063388:Endocannabinoids; D008024:Ligands; D009025:Morpholines; D009281:Naphthalenes; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D011720:Pyrazoles; D043882:Receptors, Cannabinoid; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D000077285:Rimonabant; C078814:anandamide