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

    Authors

    A. A. Alvarez; M. Field; S. Bushnev; M. S. Longo;K. Sugaya

    Comments

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    Abbreviated Journal Title

    J. Mol. Neurosci.

    Keywords

    Glioblastoma multiforme; Cancer stem cells; Histone deactylation; TrichostatinA; AMYLOID PRECURSOR PROTEIN; NEURAL PROGENITOR CELLS; QUANTITATIVE RT-PCR; REAL-TIME; MALIGNANT GLIOMAS; GENE-EXPRESSION; BRAIN-TUMORS; NEUROPROGENITOR CELLS; GLIAL DIFFERENTIATION; ADJUVANT TEMOZOLOMIDE; Biochemistry & Molecular Biology; Neurosciences

    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.

    Journal Title

    Journal of Molecular Neuroscience

    Volume

    55

    Issue/Number

    1

    Publication Date

    1-1-2015

    Document Type

    Article

    Language

    English

    First Page

    7

    Last Page

    20

    WOS Identifier

    WOS:000348341300002

    ISSN

    0895-8696

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