Vanadium and cancer treatment: Antitumoral mechanisms of three oxidovanadium(IV) complexes on a human osteosarcoma cell line

• The bioactivity of three vanadyl complexes was investigated in osteosarcoma cells.
• Compounds were screened for their anticancer activity against MG-63 cell line.
• The complexes induced cyto- and genotoxicity that caused impaired cell viability.
• Oxidative stress, apoptosis and DNA cleavage were the main mechanisms of action.
• The antitumoral potency was: VO(oda)phen > VO(oda)bipy > VO(oda).

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.

Bioactivity of three oxovanadium(IV) complexes with oxodiacetate (oda) (a multiple oxygen donor) and intercalating DNA related ligands: odabipy and odaphen, was evaluated in the human osteosarcoma cell line (MG-63). Cytotoxicity, genotoxicity, and mechanisms of action correlated with the chemical structures. VO(oda)phen was the most potent antitumoral complex of this series.Figure optionsDownload as PowerPoint slide