Retracted: Superoxide-dependent uptake of vitamin C in human glioma cells

Authors

  • Federico S. Rodríguez,

    1. Laboratory of Neurobiology and Stem Cells, Center for Advanced Microscopy CMA BIOBIO, University of Concepcion, Concepcion, Chile
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  • Katterine A. Salazar,

    1. Laboratory of Neurobiology and Stem Cells, Center for Advanced Microscopy CMA BIOBIO, University of Concepcion, Concepcion, Chile
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  • Nery A. Jara,

    1. Laboratory of Neurobiology and Stem Cells, Center for Advanced Microscopy CMA BIOBIO, University of Concepcion, Concepcion, Chile
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  • María A García-Robles,

    1. Laboratory of Cellular Biology, University of Concepcion, Concepcion, Chile
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  • Fernando Pérez,

    1. Hospital Guillermo Grant Benavente, Concepción, Chile
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  • Luciano E. Ferrada,

    1. Laboratory of Neurobiology and Stem Cells, Center for Advanced Microscopy CMA BIOBIO, University of Concepcion, Concepcion, Chile
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  • Fernando Martínez,

    1. Laboratory of Neurobiology and Stem Cells, Center for Advanced Microscopy CMA BIOBIO, University of Concepcion, Concepcion, Chile
    2. Laboratory of Cellular Biology, University of Concepcion, Concepcion, Chile
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  • Francisco J. Nualart

    Corresponding author
    1. Laboratory of Neurobiology and Stem Cells, Center for Advanced Microscopy CMA BIOBIO, University of Concepcion, Concepcion, Chile
    • Address correspondence and reprint requests to Francisco Nualart, Departamento de Biología Celular, Facultad de Ciencias Biológicas, Casilla 160-C, Universidad de Concepción, Concepción, Chile. E-mail: frnualart@udec.cl

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Errata

This article is corrected by:

  1. Errata: Retraction Volume 133, Issue 6, 935, Article first published online: 27 May 2015

Abstract

Glioblastomas are lethal brain tumors that resist current cytostatic therapies. Vitamin C may antagonize the effects of reactive oxygen species (ROS) generating therapies; however, it is often used to reduce therapy-related side effects despite its effects on therapy or tumor growth. Because the mechanisms of vitamin C uptake in gliomas are currently unknown, we evaluated the expression of the sodium-vitamin C cotransporter (SVCT) and facilitative hexose transporter (GLUT) families in human glioma cells. In addition, as microglial cells can greatly infiltrate high-grade gliomas (constituting up to 45% of cells in glioblastomas), the effect of TC620 glioma cell interactions with microglial-like HL60 cells on vitamin C uptake (Bystander effect) was determined. Although glioma cells expressed high levels of the SVCT isoform-2 (SVCT2), low functional activity, intracellular localization and the expression of the dominant-negative isoform (dnSVCT2) were observed. The increased glucose metabolic activity of glioma cells was evident by the high 2-Deoxy-d-glucose and dehydroascorbic acid (DHA) uptake rates through the GLUT isoform-1 (GLUT1), the main DHA transporter in glioblastoma. Co-culture of glioma cells and activated microglial-like HL60 cells resulted in extracellular ascorbic acid oxidation and high DHA uptake by glioma cells. This Bystander effect may explain the high antioxidative potential observed in high-grade gliomas.

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This study strongly suggests that the Bystander effect, that is, glioma cell interaction with oxidant-producing microglia, could be an important mechanism for glioma vitamin C loading in the absence of functional sodium-vitamin C cotransporter 2 (SVCT2) expression. The high cellular vitamin C load in glioma cells results from a high uptake of extracellular dehydroascorbic acid (DHA) generated by neighboring microglia. This Bystander effect may explain the high antioxidative potential observed in high-grade gliomas, considering that high-grade gliomas may be the only neoplasm where oxidant-producing microglia can almost equal the number of tumor cells.

Ancillary