Vanadate-induced cell death is dissociated from H2O2 generation

Vanadium is an environmentally toxic metal with peculiar and sometimes contradictory cellular effects. It is insulin-mimetic, it can either stimulate cell growth or induce cell death, and it has both mutagenic and antineoplastic properties. However, the mechanisms involved in those effects are poorl...

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Bibliographic Details
Published in:Cell biology and toxicology 2007-11, Vol.23 (6), p.413-420
Main Authors: Capella, M A M, Capella, L S, Valente, R C, Gefé, M, Lopes, A G
Format: Article
Language:English
Subjects:
Animals
Apoptosis
Cell Death - drug effects
Cells
Cytotoxicity
Dogs
Fluorescence
Haplorhini
Humans
Hydrogen peroxide
Hydrogen Peroxide - metabolism
Hydrogen Peroxide - pharmacology
K562 Cells
Mortality
Oxidation-Reduction - drug effects
Rhodamines - metabolism
Vanadates - toxicity
Vanadium
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Summary:Vanadium is an environmentally toxic metal with peculiar and sometimes contradictory cellular effects. It is insulin-mimetic, it can either stimulate cell growth or induce cell death, and it has both mutagenic and antineoplastic properties. However, the mechanisms involved in those effects are poorly understood. Several studies suggest that H(2)O(2) is involved in vanadate-induced cell death, but it is not known whether cellular sensitivity to vanadate is indeed related to H(2)O(2) generation. In the present study, the sensitivity of four cell lines from different origins (K562, K562-Lucena 1, MDCK, and Ma104) to vanadate and H(2)O(2) was evaluated and the production of H(2)O(2) by vanadate was analyzed by flow cytometry. We show that cell lines very resistant to H(2)O(2) (K562, K562-Lucena 1, and Ma104 cells) are much more sensitive to vanadate than MDCK, a cell line relatively susceptible to H(2)O(2), suggesting that vanadate-induced cytotoxicity is not directly related to H(2)O(2) responsiveness. In accordance, vanadate concentrations that reduced cellular viability to approximately 60-70% of the control (10 mumol/L) did not induce H(2)O(2) formation. A second hypothesis, that peroxovanadium (PV) compounds, produced once vanadate enters into the cells, are responsible for the cytotoxicity, was only partially confirmed because MDCK cells were resistant to both vanadate and PV compounds (10 micromol/L each). Therefore, our results suggest that vanadate toxicity occurs by two distinct pathways, one dependent on and one independent of H(2)O(2) production.
ISSN:0742-2091
1573-6822
DOI:10.1007/s10565-007-9003-4