Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Scheipl, S; Lohberger, B; Rinner, B; Froehlich, EV; Beham, A; Quehenberger, F; Lazáry, A; Pal Varga, P; Haybaeck, J; Leithner, A; Liegl, B.
Histone deacetylase inhibitors as potential therapeutic approaches for chordoma: an immunohistochemical and functional analysis.
J Orthop Res. 2013; 31(12):1999-2005
Doi: 10.1002/jor.22447
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- Führende Autor*innen der Med Uni Graz
- Liegl-Atzwanger Bernadette
- Scheipl Susanne
- Co-Autor*innen der Med Uni Graz
- Beham Alfred
- Fröhlich-Sorger Elke Verena
- Haybäck Johannes
- Leithner Andreas
- Lohberger Birgit
- Quehenberger Franz
- Rinner Beate
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- Abstract:
- Chordomas are rare malignancies of the axial skeleton. Therapy is mainly restricted to surgery. This study investigates histone deacetylase (HDAC) inhibitors as potential therapeutics for chordomas. Immunohistochemistry (IHC) was performed using the HDAC 1-6 antibodies on 50 chordoma samples (34 primary tumors, 16 recurrences) from 44 patients (27 male, 17 female). Pan-HDAC-inhibitors Vorinostat (SAHA), Panobinostat (LBH-589), and Belinostat (PXD101) were tested for their efficacy in the chordoma cell line MUG-Chor1 via Western blot, cell cycle analysis, caspase 3/7 activity (MUG-Chor1, UCh-1), cleaved caspase-3, and PARP cleavage. p-Values below 0.05 were considered significant. IHC was negative for HDAC1, positive for HDAC2 in most (n = 36; 72%), and for HDACs 3-6 in all specimens available (n = 43; 86%). HDAC6 expression was strongest. SAHA and LBH-589, but not PXD101 caused a significant increase of G2/M phase cells and of cleaved caspase-3 (p = 0.0003, and p = 0.0014 after 72 h, respectively), and a peak of caspase 3/7 activity. PARP cleavage confirmed apoptosis. The presented chordoma series expressed HDACs 2-6 with strongest expression of HDAC6. SAHA and LBH-589 significantly increased apoptosis and changed cell cycle distribution in vitro. HDAC-inhibitors should be further evaluated as therapeutic options for chordoma.
- Find related publications in this database (using NLM MeSH Indexing)
- Adult -
- Aged -
- Aged, 80 and over -
- Caspase 3 - metabolism
- Cell Line, Tumor -
- Chordoma - drug therapy
- Female -
- Histone Deacetylase Inhibitors - therapeutic use
- Histone Deacetylases - analysis
- Humans -
- Hydroxamic Acids - pharmacology
- Immunohistochemistry -
- Indoles - pharmacology
- Male -
- Middle Aged -
- Find related publications in this database (Keywords)
- chordoma
- HDAC
- HDAC inhibitors
- targeted therapies
- survival