The Effects Of Histone Deacetylase Inhibitors On Glioblastoma-Derived Stem Cells

Keywords

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

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.

Publication Date

1-1-2015

Publication Title

Journal of Molecular Neuroscience

Volume

55

Issue

1

Number of Pages

7-20

Document Type

Article

Personal Identifier

scopus

DOI Link

https://doi.org/10.1007/s12031-014-0329-0

Socpus ID

84929581428 (Scopus)

Source API URL

https://api.elsevier.com/content/abstract/scopus_id/84929581428

This document is currently not available here.

Share

COinS