title: Vanadium and cancer treatment: antitumoral mechanisms of three oxidovanadium(IV) complexes on a human osteosarcoma cell line.
abstract: 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 (at 2.5 μM), while VO(oda)bipy and VO(oda) showed a decrease of cell viability only at higher concentrations (at 50 and 75 μM, respectively) (p<0.01). Moreover, VO(oda)phen caused a decrease of lysosomal and mitochondrial activities at 2.5 μM, while VO(oda) and VO(oda)bipy affected neutral red uptake and mitochondrial metabolism at 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 at 2.5 and 10 μM, respectively (p<0.01). The generation of reactive oxygen species increased 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.
authors.affiliation: Cátedra de Bioquímica Patológica, Facultad Ciencias Exactas, Universidad Nacional de La Plata, 47 y 115, 1900 La Plata, Argentina; Centro de Química Inorgánica (CEQUINOR), Facultad de Ciencias Exactas, Universidad Nacional de La Plata, 47 y 115, 1900 La Plata, Argentina.
authors.forename: I E
authors.initials: IE
authors.lastname: León
authors.affiliation: Departamento de Química, Bioquímica e Farmácia, Universidade do Algarve, Campus de Gambelas, 8005-139 Faro, Portugal.
authors.forename: N
authors.initials: N
authors.lastname: Butenko
authors.affiliation: Cátedra de Bioquímica Patológica, Facultad Ciencias Exactas, Universidad Nacional de La Plata, 47 y 115, 1900 La Plata, Argentina; Centro de Química Inorgánica (CEQUINOR), Facultad de Ciencias Exactas, Universidad Nacional de La Plata, 47 y 115, 1900 La Plata, Argentina.
authors.forename: A L
authors.initials: AL
authors.lastname: Di Virgilio
authors.affiliation: Laboratorio de Investigaciones del Sistema Inmune (LISIN), Facultad Ciencias Exactas, Universidad Nacional de La Plata, 47 y 115, 1900 La Plata, Argentina.
authors.forename: C I
authors.initials: CI
authors.lastname: Muglia
authors.affiliation: Centro de Química Inorgánica (CEQUINOR), Facultad de Ciencias Exactas, Universidad Nacional de La Plata, 47 y 115, 1900 La Plata, Argentina.
authors.forename: E J
authors.initials: EJ
authors.lastname: Baran
authors.affiliation: Departamento de Química, Bioquímica e Farmácia, Universidade do Algarve, Campus de Gambelas, 8005-139 Faro, Portugal.
authors.forename: I
authors.initials: I
authors.lastname: Cavaco
authors.affiliation: Cátedra de Bioquímica Patológica, Facultad Ciencias Exactas, Universidad Nacional de La Plata, 47 y 115, 1900 La Plata, Argentina; Centro de Química Inorgánica (CEQUINOR), Facultad de Ciencias Exactas, Universidad Nacional de La Plata, 47 y 115, 1900 La Plata, Argentina. Electronic address: etcheverry@biol.unlp.edu.ar.
authors.forename: S B
authors.initials: SB
authors.lastname: Etcheverry
mesh_terms: D015082:2,2'-Dipyridyl / Q000737:chemistry*; D000085:Acetates / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D020552:Comet Assay; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000494:pharmacology*; D053938:DNA Fragmentation / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009499:Neutral Red / Q000378:metabolism; D010618:Phenanthrolines / Q000737:chemistry*; D010718:Phosphatidylserines / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D014639:Vanadium / Q000737:chemistry*
chemical_list: D000085:Acetates; D000970:Antineoplastic Agents; D056831:Coordination Complexes; D010618:Phenanthrolines; D010718:Phosphatidylserines; D017382:Reactive Oxygen Species; D014639:Vanadium; D009499:Neutral Red; D015082:2,2'-Dipyridyl
keywords: Apoptosis; Cytotoxicity; DNA damage; Human osteosarcoma cell line; Oxidovanadium(IV) complexes; Oxodiacetate