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

Cancer Lett. 2011 Jul 28;306(2):223-9. doi: 10.1016/j.canlet.2011.03.010. Epub 2011 Apr 16.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation / drug effects
  • Animals
  • Apoptosis / drug effects
  • Apoptosis / radiation effects
  • Blotting, Western
  • Cell Proliferation / drug effects
  • Cell Proliferation / radiation effects
  • Combined Modality Therapy
  • DNA Repair Enzymes / metabolism
  • Flow Cytometry
  • Forkhead Transcription Factors / physiology
  • Gamma Rays
  • Histone Deacetylase Inhibitors / therapeutic use*
  • Histone Deacetylases / chemistry
  • Histone Deacetylases / metabolism
  • Histones / metabolism
  • Humans
  • Hydroxamic Acids / therapeutic use*
  • Luminescent Proteins / metabolism
  • Mice
  • Mice, Nude
  • Neuroblastoma / drug therapy*
  • Neuroblastoma / radiotherapy*
  • Neuroblastoma / secondary
  • Radiation-Sensitizing Agents / therapeutic use*
  • Tumor Cells, Cultured
  • Tumor Stem Cell Assay
  • Vorinostat

Substances

  • Forkhead Transcription Factors
  • H2AX protein, human
  • Histone Deacetylase Inhibitors
  • Histones
  • Hydroxamic Acids
  • Luminescent Proteins
  • Radiation-Sensitizing Agents
  • Whn protein
  • Vorinostat
  • Histone Deacetylases
  • DNA Repair Enzymes

Grant support