Cannabinoid receptor ligands mediate growth inhibition and cell death in mantle cell lymphoma.
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.
Flygare
Jenny
J
Department of Laboratory Medicine, Division of Pathology, Karolinska Institutet, Karolinska University Hospital Huddinge, F-46, SE-141 86 Stockholm, Sweden.
Gustafsson
Kristin
K
Kimby
Eva
E
Christensson
Birger
B
Sander
Birgitta
B
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
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