title: Copper(II) mixed chelate compounds induce apoptosis through reactive oxygen species in neuroblastoma cell line CHP-212.
abstract: In the present work we report the antiproliferative activity of Cu(II) coordination compounds, CasIIgly ([Cu(4,7-dimethyl-1,10-phenanthroline) (glycinato) (H2O)]NO3), CasIIIia ([Cu(4,4'-dimethyl-2,2'-bipyridine) (glycinato) (H2O)]NO3), and CasIIIEa ([Cu(4,7-dimethyl-1,10-phenanthroline) (acetylacetonato) (H2O)]NO3), against human tumoral cell line CHP-212 (estromal neuroblastoma). Additionally, the molecular structure of CasIIIEa was reported. The IC50 values obtained for the evaluated compounds are in the range 18 to 47 μM, representing an inhibition potency increase of 5 to 12 times compared with cisplatin (IC50=226.7 μM). After 2h of incubation with the evaluated compounds, cells showed high levels of reactive oxygen species and a considerable GSH depletion, besides an important disruption of the mitochondrial membrane with release of cytochrome C and besides the presence of caspase-3, an effector caspase that is activated in the last step of apoptosis cascade. The results confirm that cell death in neuroblastoma CHP-212 treated with Casiopeínas occurs via apoptosis. Due to the lack of expression of caspase-8, cell death is principally by the mitochondrial pathway. Thus, one of the most interesting findings of this work is the identification of a very important damage in neuroblastoma cells induced by Cu(II) coordination compounds in a very short exposition times.
authors.affiliation: Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México D.F., Mexico.
authors.forename: Anllely Grizett
authors.initials: AG
authors.lastname: Gutiérrez
authors.forename: Adriana
authors.initials: A
authors.lastname: Vázquez-Aguirre
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: García-Ramos
authors.forename: Marcos
authors.initials: M
authors.lastname: Flores-Alamo
authors.forename: Enrique
authors.initials: E
authors.lastname: Hernández-Lemus
authors.forename: Lena
authors.initials: L
authors.lastname: Ruiz-Azuara
authors.forename: Carmen
authors.initials: C
authors.lastname: Mejía
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D053181:Caspase 8 / Q000235:genetics / Q000378:metabolism; D002413:Cations, Divalent; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000494:pharmacology*; D003300:Copper / Q000737:chemistry*; D018360:Crystallography, X-Ray; D045304:Cytochromes c / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D005978:Glutathione / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009942:Organometallic Compounds; D010618:Phenanthrolines / Q000138:chemical synthesis / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000819:agonists* / Q000378:metabolism
chemical_list: C586190:(Cu(4,4'-dimethyl-2,2'-bipyridine)(glycinato)(H2O))NO3; C586191:(Cu(4,7-dimethyl-1,10-phenanthroline)(acetylacetonato)(H2O))NO3; D000970:Antineoplastic Agents; D002413:Cations, Divalent; D056831:Coordination Complexes; D009942:Organometallic Compounds; D010618:Phenanthrolines; D017382:Reactive Oxygen Species; C505569:casiopeina II-glycine; D003300:Copper; D045304:Cytochromes c; D053148:Caspase 3; D053181:Caspase 8; D005978:Glutathione; D002945:Cisplatin
keywords: Casiopeínas; Copper(II) compounds; Glutathione; Mitochondrial apoptosis; Neuroblastoma; Reactive oxygen species