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Cancer Chemotherapy and Pharmacology

, Volume 67, Issue 2, pp 439–446 | Cite as

Histone deacetylase inhibitor (HDACI) PCI-24781 potentiates cytotoxic effects of doxorubicin in bone sarcoma cells

  • Cao Yang
  • Edwin Choy
  • Francis J. Hornicek
  • Kirkham B. Wood
  • Joseph H. Schwab
  • Xianzhe Liu
  • Henry Mankin
  • Zhenfeng Duan
Original Article

Abstract

Purpose

To better understand the mechanisms of cytotoxicity and cell death induced by HDACI PCI-24781 in bone sarcoma cells.

Methods

Four bone sarcoma cell lines were treated with PCI-24781, and the cytotoxicity was investigated. Further, accumulation of acetylated histones, p21, and PARP cleavage were evaluated in PCI-24781-treated cells. The synergistic effect of PCI-24781 to doxorubicin and its mechanism was investigated in bone sarcoma cells.

Results

MTT assay demonstrated that the growth of bone sarcoma cells was inhibited after treatment with PCI-24781. Accumulation of acetylated histones, p21, and PARP cleavage were found in PCI-24781-treated cells. Expression of DNA repair protein RAD51 was inhibited, and the expression of apoptosis protein GADD45α was induced by PCI-24781 in bone sarcoma cells. Bone sarcoma cells treated with PCI-24781 become more sensitive to doxorubicin. The caspase-3/7 activity was increased with doxorubicin and PCI-24781 treatment in these cells.

Conclusions

HDACI PCI-24781 has a synergistic effect on doxorubicin-induced apoptosis in bone sarcoma cells.

Keywords

Histone deacetylase inhibitor Chemotherapy Bone sarcoma Apoptosis 

Notes

Acknowledgments

This project was supported, in part, by a grant from the Gattegno and Wechsler funds. Support has also been provided by the Kenneth Stanton Fund. Dr. Duan is supported, in part, through a grant from Sarcoma Foundation of America, and a grant from the National Cancer Institute, NIH (Nanotechnology Platform Partnership), R01-CA119617.

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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Cao Yang
    • 1
    • 2
    • 3
  • Edwin Choy
    • 2
    • 4
  • Francis J. Hornicek
    • 1
    • 2
  • Kirkham B. Wood
    • 1
  • Joseph H. Schwab
    • 1
    • 2
  • Xianzhe Liu
    • 1
    • 2
    • 3
  • Henry Mankin
    • 1
    • 2
  • Zhenfeng Duan
    • 1
    • 2
  1. 1.Department of Orthopaedic SurgeryMassachusetts General Hospital and Harvard Medical SchoolBostonUSA
  2. 2.Sarcoma Biology Laboratory, Center for Sarcoma and Connective Tissue OncologyMassachusetts General Hospital and Harvard Medical SchoolBostonUSA
  3. 3.Department of Orthopaedic SurgeryUnion Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhanChina
  4. 4.Division of Hematology OncologyMassachusetts General Hospital and Harvard Medical SchoolBostonUSA

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