Suberoylanilide Hydroxamic Acid (SAHA) Induces Apoptosis or Autophagy-associated Cell Death in Chondrosarcoma Cell Lines

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 inv...

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Bibliographic Details
Published in:Anticancer research 2008-05, Vol.28 (3A), p.1585-1591
Main Authors: YAMAMOTO, Shunsaku, TANAKA, Kazuhiro, SAKIMURA, Riku, OKADA, Takamitsu, NAKAMURA, Tomoyuki, YAN LI, TAKASAKI, Minoru, NAKABEPPU, Yusaku, IWAMOTO, Yukihide
Format: Article
Language:English
Subjects:
Adenine - analogs & derivatives
Adenine - pharmacology
Animals
Antineoplastic Agents - pharmacology
Apoptosis - drug effects
Autophagy - drug effects
Biological and medical sciences
Cell Line, Tumor
Chondrosarcoma - drug therapy
Chondrosarcoma - enzymology
Chondrosarcoma - pathology
Diseases of the osteoarticular system
Enzyme Inhibitors - pharmacology
Female
Histone Deacetylase Inhibitors
Histone Deacetylases - metabolism
Humans
Hydroxamic Acids - pharmacology
Medical sciences
Mice
Mice, Nude
Rats
Tumors
Tumors of striated muscle and skeleton
Xenograft Model Antitumor Assays
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Summary: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.
ISSN:0250-7005
1791-7530