Cooperation of the HDAC inhibitor vorinostat and radiation in metastatic neuroblastoma: Efficacy and underlying mechanisms

Sabine Mueller, Xiaodong Yang, Theo L. Sottero, Ashley Gragg, Gautam Prasad, Mei-Yin Polley, William A. Weiss, Katherine K. Matthay, Andrew M. Davidoff, Steven G. DuBois, Daphne A. Haas-Kogan

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Histone deacetylase (HDAC) inhibitors can radiosensitize cancer cells. Radiation is critical in high-risk neuroblastoma treatment, and combinations of HDAC inhibitor vorinostat and radiation are proposed for neuroblastoma trials. Therefore, we investigated radiosensitizing effects of vorinostat in neuroblastoma. Treatment of neuroblastoma cell lines decreased cell viability and resulted in additive effects with radiation. In a murine metastatic neuroblastoma in vivo model vorinostat and radiation combinations decreased tumor volumes compared to single modality. DNA repair enzyme Ku-86 was reduced in several neuroblastoma cells treated with vorinostat. Thus, vorinostat potentiates anti-neoplastic effects of radiation in neuroblastoma possibly due to down-regulation of DNA repair enzyme Ku-86.

Original languageEnglish (US)
Pages (from-to)223-229
Number of pages7
JournalCancer Letters
Volume306
Issue number2
DOIs
StatePublished - Jul 28 2011
Externally publishedYes

Fingerprint

Histone Deacetylase Inhibitors
Neuroblastoma
Radiation
DNA Repair Enzymes
Radiation Effects
Radiation-Sensitizing Agents
vorinostat
Tumor Burden
Cell Survival
Down-Regulation
Cell Line

Keywords

  • DNA repair
  • Metastatic neuroblastoma
  • Radiation
  • Vorinostat

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Cooperation of the HDAC inhibitor vorinostat and radiation in metastatic neuroblastoma : Efficacy and underlying mechanisms. / Mueller, Sabine; Yang, Xiaodong; Sottero, Theo L.; Gragg, Ashley; Prasad, Gautam; Polley, Mei-Yin; Weiss, William A.; Matthay, Katherine K.; Davidoff, Andrew M.; DuBois, Steven G.; Haas-Kogan, Daphne A.

In: Cancer Letters, Vol. 306, No. 2, 28.07.2011, p. 223-229.

Research output: Contribution to journalArticle

Mueller, S, Yang, X, Sottero, TL, Gragg, A, Prasad, G, Polley, M-Y, Weiss, WA, Matthay, KK, Davidoff, AM, DuBois, SG & Haas-Kogan, DA 2011, 'Cooperation of the HDAC inhibitor vorinostat and radiation in metastatic neuroblastoma: Efficacy and underlying mechanisms', Cancer Letters, vol. 306, no. 2, pp. 223-229. https://doi.org/10.1016/j.canlet.2011.03.010
Mueller, Sabine ; Yang, Xiaodong ; Sottero, Theo L. ; Gragg, Ashley ; Prasad, Gautam ; Polley, Mei-Yin ; Weiss, William A. ; Matthay, Katherine K. ; Davidoff, Andrew M. ; DuBois, Steven G. ; Haas-Kogan, Daphne A. / Cooperation of the HDAC inhibitor vorinostat and radiation in metastatic neuroblastoma : Efficacy and underlying mechanisms. In: Cancer Letters. 2011 ; Vol. 306, No. 2. pp. 223-229.
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