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Tellurite-induced oxidative stress leads to cell death of murine hepatocarcinoma cells

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Abstract

Data regarding tellurium (Te) toxicity are scarce. Studies on its metabolism, performed mainly in bacteria, underline a major role of reactive oxygen species (ROS). We investigated whether tellurite undergoes redox cycling leading to ROS formation and cancer cell death. The murine hepatocarcinoma Transplantable Liver Tumor (TLT) cells were challenged with tellurite either in the presence or in the absence of different compounds as N-acetylcysteine (NAC), 3-methyladenine, BAPTA-AM, and catalase. NAC inhibition of tellurite-mediated toxicity suggested a major role of oxidative stress. Tellurite also decreased both glutathione (GSH) and ATP content by 57 and 80%, respectively. In the presence of NAC however, the levels of such markers were almost fully restored. Tellurite-mediated ROS generation was assessed both by using the fluorescent, oxidation-sensitive probe dichlorodihydrofluorescein diacetate (DCHF-DA) and electron spin resonance (ESR) spectroscopy to detect hydroxyl radical formation. Cell death occurs by a caspase-independent mechanism, as shown by the lack of caspase-3 activity and no cleavage of poly(ADP-ribose)polymerase (PARP). The presence of γ-H2AX suggests tellurite-induced DNA strand breaking, NAC being unable to counteract it. Although the calcium chelator BAPTA-AM did show no effect, the rapid phosphorylation of eIF2α suggests that, in addition to oxidative stress, an endoplasmic reticulum (ER) stress may be involved in the mechanisms leading to cell death by tellurite.

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Acknowledgements

The authors express their gratitude to Véronique Allaeys for excellent technical assistance. Financial support is gratefully acknowledged to Fondecyt Grant # 1090097 and to Vicerrectoría de Investigación y Desarrollo, Departamento de Investigaciones Científicas y Tecnológicas (DICYT), Universidad de Santiago de Chile. JMS was supported by a doctoral fellowship from MECESUP UCH407 and Becas Chile (Pasantia Doctoral en el Extranjero), Chile.

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Authors and Affiliations

  1. Laboratorio de Microbiología Molecular, Facultad de Química y Biología, Universidad de Santiago de Chile, Santiago, Chile

    Juan M. Sandoval & Claudio C. Vásquez

  2. Biomedical Magnetic Resonance Unit, Louvain Drug Research Institute, Université Catholique de Louvain, Brussels, Belgium

    Philippe Levêque & Bernard Gallez

  3. Departamento de Ciencias Químicas y Farmacéuticas, Universidad Arturo Prat, Iquique, Chile

    Pedro Buc Calderon

  4. PMNT Unit, Toxicology and Cancer Biology Research Group, Louvain Drug Research Institute, Université Catholique de Louvain, Avenue E. Mounier 73, 1200, Brussels, Belgium

    Pedro Buc Calderon

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  1. Juan M. Sandoval
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  2. Philippe Levêque
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  4. Claudio C. Vásquez
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  5. Pedro Buc Calderon
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Correspondence to Pedro Buc Calderon.

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Sandoval, J.M., Levêque, P., Gallez, B. et al. Tellurite-induced oxidative stress leads to cell death of murine hepatocarcinoma cells. Biometals 23, 623–632 (2010). https://doi.org/10.1007/s10534-010-9316-2

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  • DOI: https://doi.org/10.1007/s10534-010-9316-2

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