Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Bernhart, E; Stuendl, N; Kaltenegger, H; Windpassinger, C; Donohue, N; Leithner, A; Lohberger, B.
Histone deacetylase inhibitors vorinostat and panobinostat induce G1 cell cycle arrest and apoptosis in multidrug resistant sarcoma cell lines.
Oncotarget. 2017; 8(44):77254-77267
Doi: 10.18632/oncotarget.20460
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- Führende Autor*innen der Med Uni Graz
- Bernhart Eva Maria
- Lohberger Birgit
- Co-Autor*innen der Med Uni Graz
- Donohue Nicholas
- Eck Nicole
- Kaltenegger Heike
- Leithner Andreas
- Windpassinger Christian
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- Abstract:
- Synovial sarcoma and high grade chondrosarcoma are characterized by their lack of response to conventional cytotoxic chemotherapy, the tendency to develop lung metastases, and low survival rates. Research within the field prioritizes the development and expansion of new treatment options for dealing with unresectable or metastatic diseases. Numerous clinical trials using histone deacetylases inhibitors (HDACi) have shown specific efficacy as an active antitumor agent for treating a variety of solid tumors. However, as of yet the effect of different HDACi on synovial- and chondrosarcoma cells has not been investigated. In this study, vorinostat (SAHA), panobinostat (LBH-589), and belinostat (PXD101) decreased cell viability of synovial sarcoma (SW-982) and chondrosarcoma (SW-1353) cells in a time- and dose dependent manner and arrested SW-982 cells in the G1/S phase. Western blot analysis determined the responsible cell cycle regulator proteins. In addition, we found apoptotic induction by caspase 3/7 activity, caspase 3 cleavage, and PARP cleavage. In SW-1353 cells only SAHA showed comparable effects. Noteworthy, all HDACi tested had synergistic effects with the topoisomerase II inhibitor doxorubicin in SW-1353 chondrosarcoma cells making the cells more sensitive to the chemotherapeutic drug. Our results show for the first time that SAHA and LBH-589 reduced viability of sarcoma cells and arrested them at the G1/S checkpoint, while also inducing apoptosis and enhancing chemotherapeutic sensitivity, especially in chondrosarcoma cells. These data demonstrate the exciting potential of HDACi for use in sarcoma treatment.
- Find related publications in this database (Keywords)
- G1 cell cycle arrest
- vorinostat
- belinostat
- sarcoma
- panobinostat