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1.
J Biol Inorg Chem ; 19(1): 59-74, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24233155

ABSTRACT

Flavonoids are a large family of polyphenolic compounds synthesized by plants. They display interesting biological effects mainly related to their antioxidant properties. On the other hand, vanadium compounds also exhibit different biological and pharmacological effects in cell culture and in animal models. Since coordination of ligands to metals can improve or change the pharmacological properties, we report herein, for the first time, a detailed study of the mechanisms of action of an oxidovanadium(IV) complex with the flavonoid silibinin, Na2[VO(silibinin)2]·6H2O (VOsil), in a model of the human osteosarcoma derived cell line MG-63. The complex inhibited the viability of osteosarcoma cells in a dose-dependent manner with a greater potency than that of silibinin and oxidovanadium(IV) (p < 0.01), demonstrating the benefit of complexation. Cytotoxicity and genotoxicity studies also showed a concentration effect for VOsil. The increase in the levels of reactive oxygen species and the decrease of the ratio of the amount of reduced glutathione to the amount of oxidized glutathione were involved in the deleterious effects of the complex. Besides, the complex caused cell cycle arrest and activated caspase 3, triggering apoptosis as determined by flow cytometry. As a whole, these results show the main mechanisms of the deleterious effects of VOsil in the osteosarcoma cell line, demonstrating that this complex is a promising compound for cancer treatments.


Subject(s)
Antineoplastic Agents/pharmacology , Cell Proliferation/drug effects , Coordination Complexes/pharmacology , Osteosarcoma/drug therapy , Silymarin/pharmacology , Vanadates/pharmacology , Antineoplastic Agents/chemistry , Apoptosis/drug effects , Cell Line, Tumor , Coordination Complexes/chemistry , Humans , Osteosarcoma/pathology , Silybin , Silymarin/chemistry , Vanadates/chemistry
2.
Dalton Trans ; 42(33): 11868-80, 2013 Sep 07.
Article in English | MEDLINE | ID: mdl-23760674

ABSTRACT

Flavonoids, a polyphenolic compound family, and the vanadium compounds have interesting biological, pharmacological, and medicinal properties. We report herein the antitumor actions of the complex [VO(chrysin)2EtOH]2 (VOchrys) on the MG-63 human osteosarcoma cell line. Oxovanadium(IV), chrysin and VOchrys caused a concentration-dependent inhibition of cell viability. The complex was the strongest antiproliferative agent (p < 0.05). Cytotoxicity and genotoxicity studies also showed a concentration effect. Reactive oxygen species (ROS) and the alterations in the GSH/GSSG ratio underlie the main mechanisms of action of VOchrys. Additions of ROS scavengers (vitamin C plus vitamin E) or GSH to the viability experiments demonstrated beneficial effects (p < 0.01). Besides, the complex triggered apoptosis, disruption of the mitochondria membrane potential (MMP), increased levels of caspase 3 and DNA fragmentation measured by the sub-G1 peak in cell cycle arrest experiments (p < 0.01). Collectively, VOchrys is a cell death modulator and a promissory complex to be used in cancer treatments.


Subject(s)
Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Flavonoids/chemistry , Organometallic Compounds/pharmacology , Osteosarcoma/drug therapy , Oxidative Stress/drug effects , Vanadates/chemistry , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Humans , Molecular Structure , Organometallic Compounds/chemical synthesis , Organometallic Compounds/chemistry , Osteosarcoma/pathology , Structure-Activity Relationship
3.
Biol Trace Elem Res ; 109(2): 189-94, 2006 Feb.
Article in English | MEDLINE | ID: mdl-16444008

ABSTRACT

The interaction of the VO2+ cation with meso-2,3-dimercaptosuccinic acid (DMSA) was investigated by electron absorption spectroscopy in aqueous solution at different pH values. The spectral behavior, complemented with a spectrophotometric titration, shows the generation of a [VO(DMSA)2]2- complex in which the oxocation interacts with two pairs of deprotonated -SH groups of the acid. It was also found that DMSA rapidly reduces VO3- to VO2+, which might be chelated by an excess of the acid. DMSA can also produce the partial reduction of a V2O5 suspension at pH=5.2. The results of this study suggest that DMSA might be a potentially useful detoxification agent for vanadium.


Subject(s)
Succimer/metabolism , Vanadium/metabolism , Chelating Agents , Drug Interactions , Inactivation, Metabolic , Oxidation-Reduction , Spectroscopy, Electron Energy-Loss , Vanadates/metabolism
4.
Biol Trace Elem Res ; 105(1-3): 53-8, 2005.
Article in English | MEDLINE | ID: mdl-16034153

ABSTRACT

The interaction of the VO2+ cation with homocysteine was investigated by electron absorption spectroscopy in aqueous solution at different metal-to-ligand ratios. The direct reduction of vanadate(V) solutions with homocysteine was also investigated. The results suggest that the interaction is different from that found in the case of cysteine and occurs through pairs of amino and carboxylate groups of the amino acid. The interaction of VO2+ with homocystine, the oxidation product of homocysteine, was also analyzed. The interest of the results in relation to vanadium metabolism and detoxification is briefly discussed.


Subject(s)
Homocysteine/metabolism , Vanadates/chemistry , Vanadates/metabolism , Amino Acids/chemistry , Cations , Cysteine/chemistry , Electrons , Homocysteine/chemistry , Hydrogen-Ion Concentration , Ligands , Metals/chemistry , Models, Chemical , Spectrophotometry , Trace Elements
5.
J Inorg Biochem ; 88(1): 94-100, 2002 Jan 01.
Article in English | MEDLINE | ID: mdl-11750030

ABSTRACT

The synthesis and spectral and magnetic characterization of VO(2+) complexes with Ibuprofen (2-(4-isobutylphenyl)propionic acid), Naproxen (6-methoxy-alpha-methyl-2-naphthalene acetic acid) and Tolmetin (1-methyl-5-(4-methylbenzoyl)-1H-pyrrole-2-acetic acid) were studied. The complexes [VO(Ibu)(2)] x 5CH(3)OH, [VO(Nap)(2)] x 5CH(3)OH and [VO(Tol)(2)] were obtained from methanolic solutions under nitrogen atmosphere. The biological activities of these complexes on the proliferation of two osteoblast-like cells in culture (MC3T3E1 and UMR106) were compared with that of the vanadyl(IV) cation. The complexes exhibited different effects depending on the concentration and the cellular type, while no effect was observed for their parent drugs.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/chemical synthesis , Osteoblasts/drug effects , Vanadates/chemical synthesis , Vanadates/pharmacology , Animals , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Cell Division/drug effects , Dose-Response Relationship, Drug , Ibuprofen/chemistry , Ibuprofen/pharmacology , Mice , Naproxen/chemistry , Naproxen/pharmacology , Organometallic Compounds/chemical synthesis , Organometallic Compounds/chemistry , Organometallic Compounds/pharmacology , Rats , Spectrum Analysis , Tolmetin/chemistry , Tolmetin/pharmacology , Tumor Cells, Cultured/drug effects , Vanadates/chemistry
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