Journal of Molecular Neuroscience

, Volume 54, Issue 1, pp 27–40

Inhibitory Activities of Trichostatin A in U87 Glioblastoma Cells and Tumorsphere-Derived Cells

  • Felipe de Almeida Sassi
  • Lílian Caesar
  • Mariane Jaeger
  • Carolina Nör
  • Ana Lucia Abujamra
  • Gilberto Schwartsmann
  • Caroline Brunetto de Farias
  • Algemir Lunardi Brunetto
  • Patrícia Luciana da Costa Lopez
  • Rafael Roesler
Article

Abstract

Epigenetic alterations have been increasingly implicated in glioblastoma (GBM) pathogenesis, and epigenetic modulators including histone deacetylase inhibitors (HDACis) have been investigated as candidate therapies. GBMs are proposed to contain a subpopulation of glioblastoma stem cells (GSCs) that sustain tumor progression and therapeutic resistance and can form tumorspheres in culture. Here, we investigate the effects of the HDACi trichostatin A (TSA) in U87 GBM cultures and tumorsphere-derived cells. Using approaches that include a novel method to measure tumorsphere sizes and the area covered by spheres in GBM cultures, as well as a nuclear morphometric analysis, we show that TSA reduced proliferation and colony sizes, led to G2/M arrest, induced alterations in nuclear morphology consistent with cell senescence, and increased the protein content of GFAP, but did not affect migration, in cultured human U87 GBM cells. In cells expanded in tumorsphere assays, TSA reduced sphere formation and induced neuron-like morphological changes. The expression of stemness markers in these cells was detected by reverse transcriptase polymerase chain reaction. These findings indicate that HDACis can inhibit proliferation, survival, and tumorsphere formation, and promote differentiation of U87 GBM cells, providing further evidence for the development of HDACis as potential therapeutics against GBM.

Keywords

Histone deacetylase Chromatin Epigenetics Brain tumor stem cell Glioblastoma Brain cancer 

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Felipe de Almeida Sassi
    • 1
    • 2
  • Lílian Caesar
    • 1
    • 2
    • 3
  • Mariane Jaeger
    • 1
    • 2
  • Carolina Nör
    • 1
    • 2
  • Ana Lucia Abujamra
    • 1
    • 2
    • 3
  • Gilberto Schwartsmann
    • 1
    • 2
    • 4
  • Caroline Brunetto de Farias
    • 1
    • 2
    • 3
  • Algemir Lunardi Brunetto
    • 1
    • 2
    • 3
  • Patrícia Luciana da Costa Lopez
    • 1
    • 2
  • Rafael Roesler
    • 1
    • 2
    • 5
    • 6
  1. 1.Cancer Research Laboratory, University Hospital Research Center (CPE-HCPA)Federal University of Rio Grande do SulPorto AlegreBrazil
  2. 2.National Institute for Translational MedicinePorto AlegreBrazil
  3. 3.Children’s Cancer Institute (ICI-RS)Porto AlegreBrazil
  4. 4.Department of Internal Medicine, School of MedicineFederal University of Rio Grande do SulPorto AlegreBrazil
  5. 5.Laboratory of Neuropharmacology and Neural Tumor Biology, Department of Pharmacology, Institute for Basic Health SciencesFederal University of Rio Grande do SulPorto AlegreBrazil
  6. 6.Department of Pharmacology, Institute for Basic Health SciencesFederal University of Rio Grande do SulPorto AlegreBrazil

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