Abstract
Background: Since chondrosarcoma has a high resistance to conventional chemotherapy and radiotherapy, surgical resection is currently the only effective treatment. Histone deacetylase (HDAC) inhibitor exert anticancer effects, but have not been tested in chondrosarcoma. Materials and Methods: We investigated the phenotypic change in chondrosarcoma cells treated with SAHA by cell viability assay, Western blot, flow cytometric analysis and electron microscopy. Results: SAHA inhibited the growth of chondrosarcoma cell lines and induced apoptosis in SW1353 with a cleaved-PARP expression and sub-G1 fragmentation according to flow cytometric analysis. On the other hand, in RCS and OUMS-27, SAHA induced autophagy-associated cell death as shown by the detection of autophagosome-specific protein and specific ultrastructural morphology in the cytoplasm. In addition, SAHA significantly inhibited tumor growth in an in vivo xenograft model. Conclusion: These results suggest that SAHA might be a promising agent for performing clinically useful chemotherapy against chondrosarcomas.
Footnotes
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Abbreviations: SAHA, suberoylanilide hydroxamic acid; HDAC, histone deacetylase; TSA, trichostatin A; PARP, poly-ADP-ribose polymerase; LC3, microtubule-associated protein1 light chain3; FACS, flow cytometry analysis; Ac-H3, acetylated histone H3; Dox, doxorubicin; EFTs, Ewing's family tumors; MRP1, multidrug resistance-associated protein 1; 3-MA, 3-methyladenine.
- Received January 18, 2008.
- Revision received March 21, 2008.
- Accepted March 27, 2008.
- Copyright© 2008 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved