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Suberoylanilide hydroxamic acid (SAHA) induces apoptosis or autophagy-associated cell death in chondrosarcoma cell

Shunsaku Yamamoto1, Kazuhiro Tanaka, Riku Sakimura

  • 1Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Anticancer Research
|July 18, 2008
PubMed
Abstract

Insights

Histone deacetylase (HDAC) inhibitor SAHA shows promise for treating chondrosarcoma, a cancer resistant to traditional therapies. SAHA effectively inhibited tumor growth and induced cell death through apoptosis and autophagy in preclinical models.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Chondrosarcoma exhibits high resistance to conventional chemotherapy and radiotherapy.
  • Surgical resection remains the primary treatment modality for chondrosarcoma.
  • Histone deacetylase (HDAC) inhibitors have demonstrated anticancer effects but remain untested in chondrosarcoma.

Purpose of the Study:

  • To investigate the efficacy of SAHA, a histone deacetylase (HDAC) inhibitor, against chondrosarcoma.
  • To explore the mechanisms of cell death induced by SAHA in chondrosarcoma cells.

Main Methods:

  • Phenotypic changes in chondrosarcoma cells treated with SAHA were analyzed.
  • Methods included cell viability assays, Western blot, flow cytometry, and electron microscopy.
  • In vivo efficacy was assessed using a xenograft tumor model.

Main Results:

  • SAHA inhibited chondrosarcoma cell line growth and induced apoptosis in SW1353 cells, evidenced by cleaved-PARP and sub-G1 DNA fragmentation.
  • In RCS and OUMS-27 cell lines, SAHA triggered autophagy-associated cell death, confirmed by autophagosome markers and ultrastructural changes.
  • SAHA significantly suppressed tumor growth in an in vivo xenograft model.

Conclusions:

  • SAHA demonstrates potent anticancer activity against chondrosarcoma in vitro and in vivo.
  • SAHA induces distinct cell death pathways, including apoptosis and autophagy, in different chondrosarcoma cell lines.
  • SAHA represents a promising therapeutic agent for clinical development in chondrosarcoma treatment.

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