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 journalArticlepeer-review

49 Scopus citations

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

Keywords

  • DNA repair
  • Metastatic neuroblastoma
  • Radiation
  • Vorinostat

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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