INIQUI   05448
INSTITUTO DE INVESTIGACIONES PARA LA INDUSTRIA QUIMICA
Unidad Ejecutora - UE
artículos
Título:
Cytotoxicity of a Vanadyl(IV) Complex with a Multidentate Oxygen Donor in Osteoblast Cell Lines in Culture
Autor/es:
RIVADENEIRA J, DI VIRGILIO AL, BARRIO DA, MUGLIA CI, BRUZZONE L, ETCHEVERRY SB
Revista:
MEDICINAL CHEMISTRY
Editorial:
BENTHAM SCIENCE PUBL LTD
Referencias:
Año: 2010 vol. 6 p. 9 - 23
ISSN:
1573-4064
Resumen:
Strong
chelating ligands as oxodiacetate (oda) are model systems to study the
process of metal trapping by living organisms. Vanadium compounds
display interesting biological and pharmacological actions. In
vertebrates, vanadium is 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 cytotoxic actions in osteoblasts
as it was determined through a dose-dependent decrease in cell
proliferation, and morphological and actin alterations. The putative
mechanisms underlying VO(oda) deleterious effects were also
investigated. The complex increased the level of ROS which correlated
with a decreased in GSH/GSSG ratio. Besides, VO(oda) induced a
dissipation 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-E1 than in UMR106 cells. ERK activation was
inhibited by PD98059, Wortmanin and the ROS scavenger NAC (N-acetyl
cysteine). These results suggest that VO(oda) stimulated ERKs
phosphorylation by induction of free radicals involving kinases
upstream of ERK pathway. The inhibitory effect of the complex on cell
proliferation was partially reversed in both cell lines by NAC.
Moreover, PD98059 and Wortmanin also partially reversed the inhibition
of cell proliferation in the 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