IIFP   25103
INSTITUTO DE ESTUDIOS INMUNOLOGICOS Y FISIOPATOLOGICOS
Unidad Ejecutora - UE
artículos
Título:
Vanadium and cancer treatment: Antitumoral mechanisms of three oxidovanadium(IV) complexes on a human osteosarcoma cell line
Autor/es:
LEÓN I.; BUTENKO N; DI VIRGILIO A.L.; MUGLIA C.I.; BARAN, E. J.; CAVACO I; ETCHEVERRY, S.
Revista:
JOURNAL OF INORGANIC BIOCHEMISTRY
Editorial:
ELSEVIER SCIENCE INC
Referencias:
Lugar: Amsterdam; Año: 2014 p. 106 - 117
ISSN:
0162-0134
Resumen:
We report herein the antitumor actions of three oxidovanadium(IV) complexes on MG-63 human osteosarcoma cell line. The three complexes: VO(oda), VO(oda)bipy and VO(oda)phen (oda = oxodiacetate), caused a concentration dependent inhibition of cell viability. The antiproliferative action of VO(oda)phen could be observed in the whole range of concentrations (from at 2.5 μM), while VO(oda)bipy and VO(oda) showed a decrease of cell viability only at higher concentrations (fromat 50 and 75 μM, respectively) (p < 0.01). Moreover, VO(oda)phen caused a decrease of lysosome and mitochondrial activity fromat 2.5 μM, while VO(oda) and VO(oda)bipy affected neutral red uptake and mitochondrial metabolism fromat 50 μM (p < 0.01). On the other hand, no DNA damage studied by the Comet assay, could be observed in MG-63 cells treated with VO(oda) at 2.5-?10 μM. Nevertheless,VO(oda)phen and VO(oda)bipy induced DNA damage fromat 2.5 and 10 μM, respectively (p < 0.01). The generation of reactive oxygen species increased from at 10 μM of VO(oda)phen and only at 100 μM of VO(oda) and VO(oda)bipy (p < 0.01). Besides, VO(oda)phen and VO(oda)bipy triggered apoptosis as determined by externalization of the phosphatidylserine. The determination of DNA cleavage by agarose gel electrophoresis showed that the ability of VO(oda)(bipy) is similar to that of VO(oda), while VO(oda)(phen) showed the highest nuclease activity in this series. Overall, our results showed a good relationship between the bioactivity of the complexes and their structures since VO(oda)phen presented the most potent antitumor action in human osteosarcoma cells followed by VO(oda)bipy and then by VO(oda) according to the number of intercalating heterocyclic moieties.