CD95/CD95 ligand-independent potentiation of treosulfan cytotoxicity by BSO in malignant glioma cells in vitro and in vivo

  • Authors:
    • W. Wick
    • J. Stock
    • J. Seyfried
    • J. Baumgart
    • U. Wullner
    • M. Weller
  • View Affiliations

  • Published online on: July 1, 2002     https://doi.org/10.3892/ijo.21.1.213
  • Pages: 213-220
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Abstract

The glutathione synthase inhibitor, buthionine sulfoximine (BSO), specifically enhances the cytotoxic effects of treosulfan in human glioma cells. BSO depletes glutathione and greatly enhances treosulfan cytotoxicity in all the 12 human malignant glioma cell lines examined. None of these cell lines showed enhanced susceptibility to CD95L- or tumor necrosis factor (TNF)-α-induced apoptosis when glutathione is depleted. The combination of serial systemic BSO applications (300 mg/kg) and a single systemic dose of treosulfan (2.5 g/kg) reduced the growth of intracranially growing rat C6 gliomas in vivo by 73% whereas treosulfan alone reduced tumor growth by 16% and BSO alone had no effect. BSO lowered glutathione levels to 25-30% in peripheral blood mononuclear cells (PBMC) and to 50% in the glioma tissue. The glutathione levels in the non-tumor-bearing contralateral hemisphere were unaffected by systemic BSO treatment. The main side effects of treosulfan, gastrointestinal and bone marrow toxicity, were not significantly enhanced by BSO.

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July 2002
Volume 21 Issue 1

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Wick W, Stock J, Seyfried J, Baumgart J, Wullner U and Weller M: CD95/CD95 ligand-independent potentiation of treosulfan cytotoxicity by BSO in malignant glioma cells in vitro and in vivo. Int J Oncol 21: 213-220, 2002.
APA
Wick, W., Stock, J., Seyfried, J., Baumgart, J., Wullner, U., & Weller, M. (2002). CD95/CD95 ligand-independent potentiation of treosulfan cytotoxicity by BSO in malignant glioma cells in vitro and in vivo. International Journal of Oncology, 21, 213-220. https://doi.org/10.3892/ijo.21.1.213
MLA
Wick, W., Stock, J., Seyfried, J., Baumgart, J., Wullner, U., Weller, M."CD95/CD95 ligand-independent potentiation of treosulfan cytotoxicity by BSO in malignant glioma cells in vitro and in vivo". International Journal of Oncology 21.1 (2002): 213-220.
Chicago
Wick, W., Stock, J., Seyfried, J., Baumgart, J., Wullner, U., Weller, M."CD95/CD95 ligand-independent potentiation of treosulfan cytotoxicity by BSO in malignant glioma cells in vitro and in vivo". International Journal of Oncology 21, no. 1 (2002): 213-220. https://doi.org/10.3892/ijo.21.1.213