, Volume 24, Issue 6, pp 1153–1168 | Cite as

Cyto- and genotoxicity of a vanadyl(IV) complex with oxodiacetate in human colon adenocarcinoma (Caco-2) cells: potential use in cancer therapy

  • Ana L. Di Virgilio
  • Josefina Rivadeneira
  • Cecilia I. Muglia
  • Miguel A. Reigosa
  • Nataliya Butenko
  • Isabel Cavaco
  • Susana B. Etcheverry


The complex of vanadyl(IV) cation with oxodiacetate, VO(oda) caused an inhibitory effect on the proliferation of the human colon adenocarcinoma cell line Caco-2 in the range of 25–100 μM (P < 0.001). This inhibition was partially reversed by scavengers of free radicals. The difference in cell proliferation in the presence and the absence of scavengers was statistically significant in the range of 50–100 μM (P < 0.05). VO(oda) altered lysosomal and mitochondria metabolisms (neutral red and MTT bioassays) in a dose–response manner from 10 μM (P < 0.001). Morphological studies showed important transformations that correlated with the disassembly of actin filaments and a decrease in the number of cells in a dose response manner. Moreover, VO(oda) caused statistically significant genotoxic effects on Caco-2 cells in the low range of concentration (5–25 μM) (Comet assay). Increment in the oxidative stress and a decrease in the GSH level are the main cytotoxic mechanisms of VO(oda). These effects were partially reversed by scavengers of free radicals in the range of 50–100 μM (P < 0.05). Besides, VO(oda) interacted with plasmidic DNA causing single and double strand cleavage, probably through the action of free radical species. Altogether, these results suggest that VO(oda) is a good candidate to be evaluated for alternative therapeutics in cancer treatment.


Vanadyl(IV) cation Multidentate ligands Cytotoxicity Genotoxicity Caco-2 tumoral cells 



The authors would like to thank Prof. Dr. E.J. Baran for the preparation of VO(oda) complex and Prof. Dr. L. Bruzzone for the fluorometric measurements of DHR experiments. This work was supported by UNLP, CONICET (PIP 1125) and ANPCyT (PICT 2218), and the Erasmus Mundus Programme, EMQAL 2008-0095, for mobility funding. JR is a postdoctoral fellowship from CONICET, Argentina. ALDV, CIM and SBE are members of the Carrera del Investigador, CONICET, Argentina. MAR is a member of Carrera de Personal de Apoyo, CONICET, Argentina. NB is a doctoral student of the Erasmus Mundus External Cooperation Window—Lot 6. IC is Prof. of the Algarve University, Faro, Portugal.

Conflict of interest

The authors declare that there are no conflicts of interest.


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Copyright information

© Springer Science+Business Media, LLC. 2011

Authors and Affiliations

  • Ana L. Di Virgilio
    • 1
  • Josefina Rivadeneira
    • 1
    • 2
  • Cecilia I. Muglia
    • 1
  • Miguel A. Reigosa
    • 3
  • Nataliya Butenko
    • 4
    • 5
  • Isabel Cavaco
    • 4
    • 5
  • Susana B. Etcheverry
    • 1
    • 2
  1. 1.Cátedra de Bioquímica Patológica, Facultad de Ciencias ExactasUNLPLa PlataArgentina
  2. 2.CEQUINOR (CONICET-UNLP), Facultad de Ciencias ExactasUNLPLa PlataArgentina
  3. 3.Instituto Multidisciplinario de Biología Celular (IMBICE)La PlataArgentina
  4. 4.Departamento de Química, Bioquímica e FarmáciaUniversidade do AlgarveFaroPortugal
  5. 5.Centro de Química EstruturalInstituto Superior Técnico, TU LisbonLisbonPortugal

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