title: Cannabinoids inhibit peptidoglycan-induced phosphorylation of NF-κB             and cell growth in U87MG human malignant glioma cells.
abstract: Nuclear factor (NF)-κB is the key transcription factor involved in the inflammatory             responses, and its activation aggravates tumors. Peptidoglycan (PGN), a main cell             wall component of Gram-positive bacteria, stimulates Toll-like receptor 2 (TLR-2)             and activates a number of inflammatory pathways, including NF-κB. Cannabinoids             have been reported to exert anti-inflammatory and antitumor effects. The mechanisms             underlying these actions, however, are largely unknown. The purpose of this study             was to investigate whether cannabinoids can suppress the PGN-induced activation             of NF-κB and cell growth via cannabinoid receptors in U87MG human malignant glioma             cells. PGN treatment induced the phosphorylation of NF-κB and cell proliferation             in a concentration-dependent manner. The main endocannabinoid, 2-arachidonoylglycerol,             prevented the PGN-induced phosphorylation of NF-κB, which was reversed by the             CB1 cannabinoid receptor antagonist, AM281. The synthetic cannabinoid, WIN55,212-2,             abolished the PGN-activated cell growth, and this effect was reversed by AM281.             The preferential expression of CB1 rather than CB2 receptors in these cells was             confirmed by reverse transcription-mediated polymerase chain reaction experiments             and the observation that the WIN55,212-2-induced morphological changes were completely             reversed by AM281 but not by the CB2 antagonist, AM630. Our finding that cannabinoids             suppress the NF-κB inflammatory pathway and cell growth via CB1 receptors in glioma             cells provides evidence for the therapeutic potential of targeting cannabinoid             receptors for the treatment of inflammation-dependent tumor progression.
authors: Department of Impairment Study, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa 920-8640, Japan.
authors: Ryosuke
authors: R
authors: Echigo
authors: Naotoshi
authors: N
authors: Sugimoto
authors: Akihiro
authors: A
authors: Yachie
authors: Takako
authors: T
authors: Ohno-Shosaku
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D001095:Arachidonic Acids / Q000494:pharmacology; D048588:Benzoxazines / Q000494:pharmacology; D002186:Cannabinoids / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D016543:Central Nervous System Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D063388:Endocannabinoids / Q000494:pharmacology; D005910:Glioma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D005989:Glycerides / Q000494:pharmacology; D006801:Humans; D009025:Morpholines / Q000494:pharmacology; D016328:NF-kappa B / Q000378:metabolism*; D009281:Naphthalenes / Q000494:pharmacology; D010457:Peptidoglycan / Q000494:pharmacology*; D010766:Phosphorylation; D011720:Pyrazoles / Q000494:pharmacology; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D001095:Arachidonic Acids; D048588:Benzoxazines; D002186:Cannabinoids; D063388:Endocannabinoids; D005989:Glycerides; D009025:Morpholines; D016328:NF-kappa B; D009281:Naphthalenes; D010457:Peptidoglycan; D011720:Pyrazoles; 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; C094503:glyceryl 2-arachidonate; C109925:AM 281