title: Cannabinoids selectively inhibit proliferation and induce death of cultured human glioblastoma multiforme cells.
abstract: Normal tissue toxicity limits the efficacy of current treatment modalities for glioblastoma multiforme (GBM). We evaluated the influence of cannabinoids on cell proliferation, death, and morphology of human GBM cell lines and in primary human glial cultures, the normal cells from which GBM tumors arise. The influence of a plant derived cannabinoid agonist, Delta(9)-tetrahydrocannabinol Delta(9)-THC), and a potent synthetic cannabinoid agonist, WIN 55,212-2, were compared using time lapse microscopy. We discovered that Delta(9)-THC decreases cell proliferation and increases cell death of human GBM cells more rapidly than WIN 55,212-2. Delta(9)-THC was also more potent at inhibiting the proliferation of GBM cells compared to WIN 55,212-2. The effects of Delta(9)-THC and WIN 55,212-2 on the GBM cells were partially the result of cannabinoid receptor activation. The same concentration of Delta(9)-THC that significantly inhibits proliferation and increases death of human GBM cells has no significant impact on human primary glial cultures. Evidence of selective efficacy with WIN 55,212-2 was also observed but the selectivity was less profound, and the synthetic agonist produced a greater disruption of normal cell morphology compared to Delta(9)-THC.
authors.affiliation: California Pacific Medical Center Research Institute, 475 Brannan St., Suite 220, San Francisco, CA 94107, USA. mcallis@sutterhealth.org
authors.forename: Sean D
authors.initials: SD
authors.lastname: McAllister
authors.forename: Calvin
authors.initials: C
authors.lastname: Chan
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Taft
authors.forename: Tri
authors.initials: T
authors.lastname: Luu
authors.forename: Mary E
authors.initials: ME
authors.lastname: Abood
authors.forename: Dan H
authors.initials: DH
authors.lastname: Moore
authors.forename: Ken
authors.initials: K
authors.lastname: Aldape
authors.forename: Garret
authors.initials: G
authors.lastname: Yount
mesh_terms: D048588:Benzoxazines; D001932:Brain Neoplasms / Q000188:drug therapy*; D016923:Cell Death / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000819:agonists / Q000494:pharmacology*; D005909:Glioblastoma / Q000188:drug therapy*; D006801:Humans; D009025:Morpholines / Q000494:pharmacology*; D009281:Naphthalenes / Q000494:pharmacology*; D009457:Neuroglia / Q000187:drug effects*; D043882:Receptors, Cannabinoid / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D048588:Benzoxazines; D009025:Morpholines; D009281:Naphthalenes; 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; D013759:Dronabinol