Open Access

Acid ceramidase confers radioresistance to glioblastoma cells

  • Authors:
    • Ninh B. Doan
    • Ha S. Nguyen
    • Mona M. Al-Gizawiy
    • Wade M. Mueller
    • Roger A. Sabbadini
    • Scott D. Rand
    • Jennifer M. Connelly
    • Christopher R. Chitambar
    • Kathleen M. Schmainda
    • Shama P. Mirza
  • View Affiliations

  • Published online on: July 28, 2017     https://doi.org/10.3892/or.2017.5855
  • Pages: 1932-1940
  • Copyright: © Doan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Glioblastoma multiforme (GBM) is the most common primary, intracranial malignancy of the central nervous system. The standard treatment protocol, which involves surgical resection, and concurrent radiation with adjuvant temozolomide (TMZ), still imparts a grim prognosis. Ultimately, all GBMs exhibit recurrence or progression, developing resistance to standard treatment. This study demonstrates that GBMs acquire resistance to radiation via upregulation of acid ceramidase (ASAH1) and sphingosine‑1-phosphate (Sph-1P). Moreover, inhibition of ASAH1 and Sph-1P, either with humanized monoclonal antibodies, small molecule drugs (i.e. carmofur), or a combination of both, led to suppression of GBM cell growth. These results suggest that ASAH1 and Sph-1P may be excellent targets for the treatment of new GBMs and recurrent GBMs, especially since the latter overexpresses ASAH1.
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October-2017
Volume 38 Issue 4

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Copy and paste a formatted citation
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Spandidos Publications style
Doan NB, Nguyen HS, Al-Gizawiy MM, Mueller WM, Sabbadini RA, Rand SD, Connelly JM, Chitambar CR, Schmainda KM, Mirza SP, Mirza SP, et al: Acid ceramidase confers radioresistance to glioblastoma cells. Oncol Rep 38: 1932-1940, 2017
APA
Doan, N.B., Nguyen, H.S., Al-Gizawiy, M.M., Mueller, W.M., Sabbadini, R.A., Rand, S.D. ... Mirza, S.P. (2017). Acid ceramidase confers radioresistance to glioblastoma cells. Oncology Reports, 38, 1932-1940. https://doi.org/10.3892/or.2017.5855
MLA
Doan, N. B., Nguyen, H. S., Al-Gizawiy, M. M., Mueller, W. M., Sabbadini, R. A., Rand, S. D., Connelly, J. M., Chitambar, C. R., Schmainda, K. M., Mirza, S. P."Acid ceramidase confers radioresistance to glioblastoma cells". Oncology Reports 38.4 (2017): 1932-1940.
Chicago
Doan, N. B., Nguyen, H. S., Al-Gizawiy, M. M., Mueller, W. M., Sabbadini, R. A., Rand, S. D., Connelly, J. M., Chitambar, C. R., Schmainda, K. M., Mirza, S. P."Acid ceramidase confers radioresistance to glioblastoma cells". Oncology Reports 38, no. 4 (2017): 1932-1940. https://doi.org/10.3892/or.2017.5855