Histone deacetylase inhibitors repress chondrosarcoma cell proliferation.

Abstract

PURPOSE:

Due to the high resistance to conventional therapy, there is still no convincingly effective treatment for chondrosarcoma. As a promising new treatment strategy, histone deacetylase inhibitors (HDACIs) have been reported to induce cell arrest, apoptosis and differentiation in some kinds of malignancies, but how HDACi exert their effects on chondrosarcoma is not well understood yet.

METHODS:

We investigated the effects of HDACIs trichostatin A (TSA) and sodium valproate (VPA) on chondrosarcoma cells in vitro and in vivo. The cell proliferation and cell cycle were examined in two chondrosarcoma cell lines, SW1353 and JJ012, by MTS and flow cytometry assays, respectively. The in vivo effects of HDACIs were investigated by assessing the chondrosarcoma growth in a mouse xenograft model.

RESULTS:

Our results showed that TSA and VPA significantly repressed the proliferation of chondrosarcoma cells in a concentration-dependent manner. Flow cytometry indicated that TSA arrested the cell cycle in G2/M phase and VPA arrested the cell cycle in G1 phase. The tumor growth was markedly suppressed in mice treated with TSA and VPA.

CONCLUSIONS:

HDACIs significantly repress the proliferation of chondrosarcoma cells in vitro and in vivo. Our findings imply that HDACIs may provide a novel therapeutic target for the treatment of chondrosarcoma.

• Authors: Jiaxue Zhu, Jianhua Gu, Jie Ma, Zhixing Xu, Hairong Tao
• Journal: Journal of B.U.ON. : official journal of the Balkan Union of Oncology (J BUON) 2015 Jan-Feb Vol. 20 Issue 1 Pg. 269-74 ISSN: 1107-0625 [Print] Cyprus
• PMID: 25778327 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Histone Deacetylase Inhibitors
• Hydroxamic Acids
• trichostatin A
• Valproic Acid
• Histone Deacetylases

Topics

• Animals
• Antineoplastic Agents (pharmacology)
• Bone Neoplasms (drug therapy, enzymology, pathology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Chondrosarcoma (drug therapy, enzymology, pathology)
• Dose-Response Relationship, Drug
• G1 Phase Cell Cycle Checkpoints (drug effects)
• G2 Phase Cell Cycle Checkpoints (drug effects)
• Histone Deacetylase Inhibitors (pharmacology)
• Histone Deacetylases (metabolism)
• Humans
• Hydroxamic Acids (pharmacology)
• Mice, Nude
• Signal Transduction (drug effects)
• Time Factors
• Tumor Burden (drug effects)
• Valproic Acid (pharmacology)
• Xenograft Model Antitumor Assays