CEQUINOR   05415
CENTRO DE QUIMICA INORGANICA "DR. PEDRO J. AYMONINO"
Unidad Ejecutora - UE
artículos
Título:
Hydroxylamido/ amino acid complexes of oxovanadium(V). Toxicological study in cell culture and in a zebrafish model.
Autor/es:
LEÓN IE; DI BIRGILIO AL; BARRIO DA; ARRAMBIDE G; GAMBINO D; ETCHEVERRY SB
Revista:
METALLOMICS
Editorial:
ROYAL SOC CHEMISTRY
Referencias:
Lugar: CAMBRIDGE; Año: 2012 vol. 4 p. 1287 - 1296
ISSN:
1756-5901
Resumen:
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Oxovanadium(V) complexes [VO(NH2O)2(val)] and [VO(NH2O)2(met)] caused inhibition of cell
proliferation in two osteoblast cell lines, MC3T3-E1 and UMR106, as well as the viability of
zebrafish eggs. In MC3T3-E1, both compounds inhibited cell proliferation (up to ca. 40% at
25 mM [VO(NH2O)2(val)] and 25% at 25 mM [VO(NH2O)2(met)]). This effect occurs in a dose
response manner from 2.5 mM (p o 0.01) with a more deleterious action of [VO(NH2O)2(met)].
In UMR106 tumoral cells, [VO(NH2O)2(val)] inhibited cell proliferation up to 75% from 25 mM
while [VO(NH2O)2(met)] behaved as an inhibitory agent in the whole range of concentrations
(p o 0.01). Similar toxic effects were obtained from morphological studies in cell cultures.
Moreover, the IC50 values for both complexes in culture studies correlated with the IC50 values
obtained with an in vivo model of toxicity (FET test). Besides, the cytotoxicity evaluation in cell
culture showed a decrease in mitochondrial activity which was stronger for [VO(NH2O)2(met)]
than for [VO(NH2O)2(val)] (44% vs. 58% at 25 mM) in both cell lines (p o 0.001). Genotoxicity
assessed by micronuclei induction also showed a stronger effect of [VO(NH2O)2(met)] in both cell
lines. Besides, [VO(NH2O)2(val)] caused DNA damage determined by comet formation in
MC3T3-E1 cells in the range of 2.525 mM, while this effect could not be observed in the
osteosarcoma cells. On the other hand, [VO(NH2O)2(val)] enhanced ROS levels over basal up to
225% and 170% at 100 mM in MC3T3-E1 and UMR106 cells, respectively (p o 0.01). For
[VO(NH2O)2(met)] a similar situation was observed, suggesting an important role for oxidative
stress in the toxicity mechanism of action. Although both complexes showed interesting results
that would deserve further drug development [VO(NH2O)2(val)] was more stable than
[VO(NH2O)2(met)] in the solid state. Therefore, we consider that [VO(NH2O)2(val)] is a good
candidate to be tested in in vivo models as a potential antitumoral agent. <!-- /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal {mso-style-parent:""; margin:0cm; margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:12.0pt; font-family:"Times New Roman"; mso-fareast-font-family:"Times New Roman"; mso-ansi-language:EN-US;} @page Section1 {size:612.0pt 792.0pt; margin:70.85pt 3.0cm 70.85pt 3.0cm; mso-header-margin:36.0pt; mso-footer-margin:36.0pt; mso-paper-source:0;} div.Section1 {page:Section1;} --> <!-- /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal {mso-style-parent:""; margin:0cm; margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:12.0pt; font-family:"Times New Roman"; mso-fareast-font-family:"Times New Roman"; mso-ansi-language:EN-US;} @page Section1 {size:612.0pt 792.0pt; margin:70.85pt 3.0cm 70.85pt 3.0cm; mso-header-margin:36.0pt; mso-footer-margin:36.0pt; mso-paper-source:0;} div.Section1 {page:Section1;} --> <!-- /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal {mso-style-parent:""; margin:0cm; margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:12.0pt; font-family:"Times New Roman"; mso-fareast-font-family:"Times New Roman"; mso-ansi-language:EN-US;} @page Section1 {size:612.0pt 792.0pt; margin:70.85pt 3.0cm 70.85pt 3.0cm; mso-header-margin:36.0pt; mso-footer-margin:36.0pt; mso-paper-source:0;} div.Section1 {page:Section1;} --> <!-- /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal {mso-style-parent:""; margin:0cm; margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:12.0pt; font-family:"Times New Roman"; mso-fareast-font-family:"Times New Roman"; mso-ansi-language:EN-US;} @page Section1 {size:612.0pt 792.0pt; margin:70.85pt 3.0cm 70.85pt 3.0cm; mso-header-margin:36.0pt; mso-footer-margin:36.0pt; mso-paper-source:0;} div.Section1 {page:Section1;} --> <!-- /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal {mso-style-parent:""; margin:0cm; margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:12.0pt; font-family:"Times New Roman"; mso-fareast-font-family:"Times New Roman"; mso-ansi-language:EN-US;} @page Section1 {size:612.0pt 792.0pt; margin:70.85pt 3.0cm 70.85pt 3.0cm; mso-header-margin:36.0pt; mso-footer-margin:36.0pt; mso-paper-source:0;} div.Section1 {page:Section1;} -->