Valproic acid promotes radiosensitization in meningioma stem-like cells

Oncotarget. 2015 Apr 30;6(12):9959-69. doi: 10.18632/oncotarget.3692.

Abstract

Although meningioma stem-like cells have been isolated and characterized, their therapeutic targeting remains a challenge. Meningioma sphere cells (MgSCs) with cancer stem cells properties show chemo- and radioresistance in comparison with meningioma adherent cells (MgACs). We tested the effect of valproic acid (VPA), a commonly used anti-epileptic drug, which passes the blood brain barrier, on cultured MgSCs. VPA reduced the viability of MgSCs and MgACs. In MgSCs, treatment with VPA increased radio-sensitivity, expression of p-cdc2, p-H2AX and cleaved caspase-3 and PARP. Anchorage-independent growth (AIG) was reduced by VPA. AIG was further reduced by combined treatment with irradiation. Expression of a stem cell marker, Oct4, was reduced by VPA. Oct4 was further decreased by combined treatment with irradiation. These results suggest that VPA may be a potential treatment for meningioma through targeting meningioma stem-like cells.

Keywords: Oct4; meningioma; radiosensitization; tumor stem-like cells; valproic acid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Apoptosis / radiation effects
  • Cell Cycle Checkpoints / drug effects
  • Cell Cycle Checkpoints / radiation effects
  • Cell Differentiation / drug effects
  • Cell Differentiation / radiation effects
  • Down-Regulation / drug effects
  • Down-Regulation / radiation effects
  • Humans
  • Meningioma / drug therapy*
  • Meningioma / pathology
  • Meningioma / radiotherapy*
  • Neoplastic Stem Cells / drug effects*
  • Neoplastic Stem Cells / radiation effects*
  • Octamer Transcription Factor-3 / biosynthesis
  • Radiation Tolerance / drug effects
  • Valproic Acid / pharmacology*

Substances

  • Octamer Transcription Factor-3
  • POU5F1 protein, human
  • Valproic Acid