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J Inorg Biochem ; 126: 17-25, 2013 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-23727332

RESUMEN

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.


Asunto(s)
Antineoplásicos/farmacología , Complejos de Coordinación/farmacología , Cobre/química , Fenantrolinas/farmacología , Especies Reactivas de Oxígeno/agonistas , Antineoplásicos/síntesis química , Apoptosis/efectos de los fármacos , Caspasa 3/genética , Caspasa 3/metabolismo , Caspasa 8/genética , Caspasa 8/metabolismo , Cationes Bivalentes , Línea Celular Tumoral , Cisplatino/farmacología , Complejos de Coordinación/síntesis química , Cristalografía por Rayos X , Citocromos c/metabolismo , Regulación Neoplásica de la Expresión Génica , Glutatión/antagonistas & inhibidores , Glutatión/metabolismo , Humanos , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Mitocondrias/patología , Compuestos Organometálicos , Fenantrolinas/síntesis química , Especies Reactivas de Oxígeno/metabolismo
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