The Effects of Histone Deacetylase Inhibitors on Glioblastoma-Derived Stem Cells

Angel A. Alvarez, Melvin Field, Sergey Bushnev, Matthew S. Longo, Kiminobu Sugaya*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

Glioblastoma multiforme (GBM) is the most malignant brain tumor with limited effective treatment options. Cancer stem cells (CSCs), a subpopulation of cancer cells with stem cell properties found in GBMs, have been shown to be extremely resistant to radiation and chemotherapeutic agents and have the ability to readily reform tumors. Therefore, the development of therapeutic agents targeting CSCs is extremely important. In this study, we isolated glioblastoma-derived stem cells (GDSCs) from GBM tissue removed from patients during surgery and analyzed their gene expression using quantitative real-time PCR and immunocytochemistry. We examined the effects of histone deacetylase inhibitors trichostatin A (TSA) and valproic acid (VPA) on the proliferation and gene expression profiles of GDSCs. The GDSCs expressed significantly higher levels of both neural and embryonic stem cell markers compared to GBM cells expanded in conventional monolayer cultures. Treatment of GDSCs with histone deacetylase inhibitors, TSA and VPA, significantly reduced proliferation rates of the cells and expression of the stem cell markers, indicating differentiation of the cells. Since differentiation into GBM makes them susceptible to the conventional cancer treatments, we posit that use of histone deacetylase inhibitors may increase efficacy of the conventional cancer treatments for eliminating GDSCs.

Original languageEnglish (US)
Pages (from-to)7-20
Number of pages14
JournalJournal of Molecular Neuroscience
Volume55
Issue number1
DOIs
StatePublished - Jan 2014

Keywords

  • Cancer stem cells
  • Glioblastoma multiforme
  • Histone deactylation
  • Trichostatin A

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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