The histone deacetylase inhibitor sodium butyrate promotes cell death and differentiation and reduces neurosphere formation in human medulloblastoma cells

Mol Neurobiol. 2013 Dec;48(3):533-43. doi: 10.1007/s12035-013-8441-7. Epub 2013 Mar 21.


Increasing evidence suggests that alterations in epigenetic mechanisms regulating chromatin state play a role in the pathogenesis of medulloblastoma (MB), the most common malignant brain tumor of childhood. Histone deacetylase (HDAC) inhibitors, which increase chromatin relaxation, have been shown to display anticancer activities. Here we show that the HDAC inhibitor sodium butyrate (NaB) markedly increases cell death and reduces colony formation in human MB cell lines. In addition, NaB increased the mRNA expression of Gria2, a neuronal differentiation marker, in D283 and DAOY cells and reduced the number of neurospheres in D283 cell cultures. Finally, NaB reduced the viability of D283 cells when combined with etoposide. These data show that NaB displays pronounced inhibitory effects on the survival of human MB cells and suggest that NaB might potentiate the effects of etoposide. In addition, our study suggests that HDAC inhibition might promote the neuronal differentiation of MB cells and provides the first evidence that an HDAC inhibitor might suppress the expansion or survival of MB cancer stem cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / metabolism
  • Brain Neoplasms / genetics
  • Brain Neoplasms / pathology*
  • Butyric Acid / pharmacology*
  • Cell Death / drug effects
  • Cell Death / genetics
  • Cell Differentiation / drug effects*
  • Cell Differentiation / genetics
  • Cell Survival / drug effects
  • Cell Survival / genetics
  • Etoposide / pharmacology
  • Gene Expression Regulation, Neoplastic / drug effects
  • Histone Deacetylase Inhibitors / pharmacology*
  • Humans
  • Medulloblastoma / genetics
  • Medulloblastoma / pathology*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Spheroids, Cellular / drug effects
  • Spheroids, Cellular / metabolism
  • Spheroids, Cellular / pathology*
  • Tumor Cells, Cultured
  • Tumor Stem Cell Assay


  • Biomarkers, Tumor
  • Histone Deacetylase Inhibitors
  • RNA, Messenger
  • Butyric Acid
  • Etoposide