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.