Artículo
Cytotoxicity of a vanadyl(IV) complex with a multidentate oxygen donor in osteoblast cell lines in culture
Rivadeneira, Josefina
; Di Virgilio, Ana Laura
; Barrio, Daniel Alejandro
; Muglia, Cecilia Isabel
; Bruzzone, L.; Etcheverry, Susana Beatriz
Fecha de publicación:
04/2010
Editorial:
Bentham Science Publishers
Revista:
Medicinal Chemistry
ISSN:
1573-4064
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
Strong chelating ligands as oxodiacetate (oda) are model systems to study the process of metal trapping by livingorganisms. Vanadium compounds display interesting biological and pharmacological actions. In vertebrates, vanadiumis stored mainly in bones. In the present study we report the effects of the complex of oda with vanadyl(IV) cation,VO(oda), on two osteoblast cell lines, one normal (MC3T3-E1) and the other tumoral (UMR106). VO(oda) exerted cytotoxicactions in osteoblasts as it was determined through a dose-dependent decrease in cell proliferation, and morphologicaland actin alterations. The putative mechanisms underlying VO(oda) deleterious effects were also investigated. Thecomplex increased the level of ROS which correlated with a decreased in GSH/GSSG ratio. Besides, VO(oda) induced adissipation of the mitochondria membrane potential (MMP) and promoted an increase in ERK cascade phosphorylation,which is involved in the regulation of cellular death and survival. All the effects were more pronounced in MC3T3-E1than in UMR106 cells. ERK activation was inhibited by PD98059, Wortmanin and the ROS scavenger NAC (N-acetylcysteine). These results suggest that VO(oda) stimulated ERKs phosphorylation by induction of free radicals involvingkinases upstream of ERK pathway. The inhibitory effect of the complex on cell proliferation was partially reversed inboth cell lines by NAC. Moreover, PD98059 and Wortmanin also partially reversed the inhibition of cell proliferation inthe tumoral osteoblasts. The use of specific inhibitors and ROS scavengers suggested the involvement of oxidative stress,MMP alterations and ERK pathway in the apoptotic actions of this complex.
Palabras clave:
VANADYL(IV)
,
MULTIDENTATE LIGAND
,
CYTOTOXICITY
,
OSTEOBLASTS
Archivos asociados
Licencia
Identificadores
Colecciones
Articulos(CCT - LA PLATA)
Articulos de CTRO.CIENTIFICO TECNOL.CONICET - LA PLATA
Articulos de CTRO.CIENTIFICO TECNOL.CONICET - LA PLATA
Articulos(CEQUINOR)
Articulos de CENTRO DE QUIMICA INORGANICA "DR. PEDRO J. AYMONINO"
Articulos de CENTRO DE QUIMICA INORGANICA "DR. PEDRO J. AYMONINO"
Articulos(INIFTA)
Articulos de INST.DE INV.FISICOQUIMICAS TEORICAS Y APLIC.
Articulos de INST.DE INV.FISICOQUIMICAS TEORICAS Y APLIC.
Citación
Rivadeneira, Josefina; Di Virgilio, Ana Laura; Barrio, Daniel Alejandro; Muglia, Cecilia Isabel; Bruzzone, L.; et al.; Cytotoxicity of a vanadyl(IV) complex with a multidentate oxygen donor in osteoblast cell lines in culture; Bentham Science Publishers; Medicinal Chemistry; 6; 1; 4-2010; 9-23
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