Cannabinoid receptor ligands mediate growth inhibition and cell death in mantle cell lymphoma |
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Authors: | Flygare Jenny Gustafsson Kristin Kimby Eva Christensson Birger Sander Birgitta |
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Affiliation: | Department of Laboratory Medicine, Division of Pathology, Karolinska Institutet, Karolinska University Hospital Huddinge, F-46, SE-141 86 Stockholm, Sweden. |
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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. |
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Keywords: | MCL, mantle cell lymphoma CB1, cannabinoid receptor type 1 CB2, cannabinoid receptor type 2 Win-55,212-2, (R)-(+)-Win-55,212-2 (2,3 dihydro)-5-methyl-3 [(morpholinyl)-methyl]pyrollo (1,2,3 de)-1,4-benzoxazinyl]-[1-naphthaleny]methanone anandamide, arachidonic acid N-(hydroxyethyl)amide DAPI, 4′,6-diamidino-2-phenylindole MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide PI, propidium iodide |
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