title: On the effects of CP 55-940 and other cannabinoid receptor agonists in C6 and U373 cell lines.
abstract: Cannabinoid receptor (CBs) agonists affect the growth of tumor cells via activation of deadly cascades. The spectrum of action of these agents and the precise role of the endocannabinoid system (ECS) on oncogenic processes remain elusive. Herein we compared the effects of synthetic (CP 55-940 and WIN 55,212-2) and endogenous (anandamide or AEA) CBs agonists (10-20 μM) on morphological changes, cell viability, and induction of apoptosis in primary astrocytes and in two glioblastoma cell lines (C6 and U373 cells) in order to characterize their possible differential actions on brain tumor cells. None of the CBs agonist tested induced changes in cell viability or morphology in primary astrocytes. In contrast, CP 55-940 significantly decreased cell viability in C6 and U373 cells at 5 days of treatment, whereas AEA and WIN 55,212-2 moderately decreased cell viability in both cell lines. Treatment of U373 and C6 for 3 and 5 days with AEA or WIN 55,212-2 produced discrete morphological changes in cell bodies, whereas the exposure to CP 55-940 induced soma degradation. CP 55-940 also induced apoptosis in both C6 and U373 cell lines. Our results support a more effective action of CP 55-940 to produce cell death of both cell lines through apoptotic mechanisms. Comparative aspects between cannabinoids with different profiles are necessary for the design of potential treatments against glial tumors.
authors.affiliation: Laboratorio de Medicina Translacional, Instituto Nacional de Cancerología, SSA, Mexico City 14080, Mexico.
authors.forename: A
authors.initials: A
authors.lastname: Ortega
authors.affiliation: Laboratorio de Aminoácidos Excitadores, Instituto Nacional de Neurología y Neurocirugía, SSA, Mexico City 14269, Mexico.
authors.forename: E
authors.initials: E
authors.lastname: Rangel-López
authors.affiliation: Laboratorio de Genómica del Cáncer, Instituto Nacional de Medicina Genómica, SSA, Mexico City 14610, Mexico.
authors.forename: A
authors.initials: A
authors.lastname: Hidalgo-Miranda
authors.affiliation: Laboratorio de Medicina Translacional, Instituto Nacional de Cancerología, SSA, Mexico City 14080, Mexico.
authors.forename: A
authors.initials: A
authors.lastname: Morales
authors.affiliation: Laboratorio de Medicina Translacional, Instituto Nacional de Cancerología, SSA, Mexico City 14080, Mexico.
authors.forename: E
authors.initials: E
authors.lastname: Ruiz-García
authors.affiliation: Laboratorio de Medicina Translacional, Instituto Nacional de Cancerología, SSA, Mexico City 14080, Mexico.
authors.forename: A
authors.initials: A
authors.lastname: Meneses-García
authors.affiliation: Laboratorio de Medicina Translacional, Instituto Nacional de Cancerología, SSA, Mexico City 14080, Mexico.
authors.forename: A
authors.initials: A
authors.lastname: Herrera-Gómez
authors.affiliation: Laboratorio de Medicina Translacional, Instituto Nacional de Cancerología, SSA, Mexico City 14080, Mexico.
authors.forename: J L
authors.initials: JL
authors.lastname: Aguilar-Ponce
authors.affiliation: Laboratorio de Aminoácidos Excitadores, Instituto Nacional de Neurología y Neurocirugía, SSA, Mexico City 14269, Mexico.
authors.forename: I G
authors.initials: IG
authors.lastname: González-Herrera
authors.affiliation: Departamento de Neuroinmunología, Instituto Nacional de Neurología y Neurocirugía, SSA, Mexico City 14269, Mexico.
authors.forename: P
authors.initials: P
authors.lastname: Guevara-Salazar
authors.affiliation: Departamento de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de Mexico, Mexico City 04510, Mexico.
authors.forename: O
authors.initials: O
authors.lastname: Prospero-García
authors.affiliation: Laboratorio de Aminoácidos Excitadores, Instituto Nacional de Neurología y Neurocirugía, SSA, Mexico City 14269, Mexico. Electronic address: absada@yahoo.com.
authors.forename: S A
authors.initials: SA
authors.lastname: Del Angel
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001095:Arachidonic Acids / Q000494:pharmacology; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects; D048588:Benzoxazines / Q000494:pharmacology; D063386:Cannabinoid Receptor Agonists / Q000494:pharmacology*; D002186:Cannabinoids / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003511:Cyclohexanols / Q000494:pharmacology; D004247:DNA; D063388:Endocannabinoids / Q000494:pharmacology; D006801:Humans; D009025:Morpholines / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D053284:Polyunsaturated Alkamides / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D001095:Arachidonic Acids; D048588:Benzoxazines; D063386:Cannabinoid Receptor Agonists; D002186:Cannabinoids; D003511:Cyclohexanols; D063388:Endocannabinoids; D009025:Morpholines; D009281:Naphthalenes; D053284:Polyunsaturated Alkamides; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; C054649:3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol; D004247:DNA; C078814:anandamide
keywords: Antiproliferative activity; Apoptosis; Cannabinoids; Glial tumors