Histone deacetylase inhibitors induce cell death and enhance the susceptibility to ionizing radiation, etoposide, and TRAIL in medulloblastoma cells

  • Authors:
    • Jürgen Sonnemann
    • K. Saravana Kumar
    • Sandra Heesch
    • Cornelia Müller
    • Christoph Hartwig
    • Manfred Maass
    • Peter Bader
    • James F. Beck
  • View Affiliations

  • Published online on: March 1, 2006     https://doi.org/10.3892/ijo.28.3.755
  • Pages: 755-766
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Abstract

Histone deacetylase inhibitors (HDIs) are a promising new class of antineoplastic agents with the ability to induce apoptosis and growth arrest of cancer cells. In addition, HDIs have been suggested to enhance the anticancer efficacy of other therapeutic regimens, such as ionizing radiation (IR) or chemotherapy. The objective of this study was to evaluate the activity of HDIs against medulloblastoma cells when applied either as single agents or in combination with IR, cytostatics, or TRAIL. The HDIs, suberoyl anilide hydroxamic acid (SAHA), sodium butyrate, and trichostatin A, were examined for their effects on the medulloblastoma cell lines, DAOY and UW228-2. We found that treatment with HDIs induced the dissipation of mitochondrial membrane potential, activation of caspase-9 and -3 and, consequently, apoptotic cell death. Moreover, all three HDIs significantly enhanced the cytotoxic effects of IR in DAOY cells. Likewise, treatment with SAHA markedly augmented the cytotoxicity of etoposide, while it had no effect on vincristine-mediated cell death. HDIs also potently increased the killing efficiency of TRAIL. TRAIL-induced, but not SAHA-induced, cell killing could be prevented by the caspase-8 inhibitor, z-IEDT-fmk. We conclude that HDIs may be useful for the treatment of medulloblastoma as monotherapy and particularly when given in combination with IR, appropriate cytostatics, or TRAIL.

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March 2006
Volume 28 Issue 3

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

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Spandidos Publications style
Sonnemann J, Kumar KS, Heesch S, Müller C, Hartwig C, Maass M, Bader P and Beck JF: Histone deacetylase inhibitors induce cell death and enhance the susceptibility to ionizing radiation, etoposide, and TRAIL in medulloblastoma cells. Int J Oncol 28: 755-766, 2006
APA
Sonnemann, J., Kumar, K.S., Heesch, S., Müller, C., Hartwig, C., Maass, M. ... Beck, J.F. (2006). Histone deacetylase inhibitors induce cell death and enhance the susceptibility to ionizing radiation, etoposide, and TRAIL in medulloblastoma cells. International Journal of Oncology, 28, 755-766. https://doi.org/10.3892/ijo.28.3.755
MLA
Sonnemann, J., Kumar, K. S., Heesch, S., Müller, C., Hartwig, C., Maass, M., Bader, P., Beck, J. F."Histone deacetylase inhibitors induce cell death and enhance the susceptibility to ionizing radiation, etoposide, and TRAIL in medulloblastoma cells". International Journal of Oncology 28.3 (2006): 755-766.
Chicago
Sonnemann, J., Kumar, K. S., Heesch, S., Müller, C., Hartwig, C., Maass, M., Bader, P., Beck, J. F."Histone deacetylase inhibitors induce cell death and enhance the susceptibility to ionizing radiation, etoposide, and TRAIL in medulloblastoma cells". International Journal of Oncology 28, no. 3 (2006): 755-766. https://doi.org/10.3892/ijo.28.3.755