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Hydroxylamido-amino acid complexes of oxovanadium(v). Toxicological study in cell culture and in a zebrafish model.
MedLine Citation:
PMID:  23073485     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Oxovanadium(v) complexes [VO(NH(2)O)(2)(val)] and [VO(NH(2)O)(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 μM [VO(NH(2)O)(2)(val)] and 25% at 25 μM [VO(NH(2)O)(2)(met)]). This effect occurs in a dose response manner from 2.5 μM (p < 0.01) with a more deleterious action of [VO(NH(2)O)(2)(met)]. In UMR106 tumoral cells, [VO(NH(2)O)(2)(val)] inhibited cell proliferation up to 75% from 25 μM while [VO(NH(2)O)(2)(met)] behaved as an inhibitory agent in the whole range of concentrations (p < 0.01). Similar toxic effects were obtained from morphological studies in cell cultures. Moreover, the IC(50) values for both complexes in culture studies correlated with the IC(50) 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(NH(2)O)(2)(met)] than for [VO(NH(2)O)(2)(val)] (44% vs. 58% at 25 μM) in both cell lines (p < 0.001). Genotoxicity assessed by micronuclei induction also showed a stronger effect of [VO(NH(2)O)(2)(met)] in both cell lines. Besides, [VO(NH(2)O)(2)(val)] caused DNA damage determined by comet formation in MC3T3-E1 cells in the range of 2.5-25 μM, while this effect could not be observed in the osteosarcoma cells. On the other hand, [VO(NH(2)O)(2)(val)] enhanced ROS levels over basal up to 225% and 170% at 100 μM in MC3T3-E1 and UMR106 cells, respectively (p < 0.01). For [VO(NH(2)O)(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(NH(2)O)(2)(val)] was more stable than [VO(NH(2)O)(2)(met)] in the solid state. Therefore, we consider that [VO(NH(2)O)(2)(val)] is a good candidate to be tested in in vivo models as a potential antitumoral agent.
Authors:
Ignacio E León; Ana L Di Virgilio; Daniel A Barrio; Gabriel Arrambide; Dinorah Gambino; Susana B Etcheverry
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-10-16
Journal Detail:
Title:  Metallomics : integrated biometal science     Volume:  -     ISSN:  1756-591X     ISO Abbreviation:  Metallomics     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-17     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101478346     Medline TA:  Metallomics     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Cátedra de Bioquímica Patológica and CEQUINOR, Facultad Ciencias Exactas, Universidad Nacional de La Plata, 47 y 115 (1900) La Plata, Argentina.
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