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

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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.

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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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Correspondence to Zhenfeng Duan.

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Yang, C., Choy, E., Hornicek, F.J. et al. Histone deacetylase inhibitor (HDACI) PCI-24781 potentiates cytotoxic effects of doxorubicin in bone sarcoma cells. Cancer Chemother Pharmacol 67, 439–446 (2011). https://doi.org/10.1007/s00280-010-1344-7

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  • DOI: https://doi.org/10.1007/s00280-010-1344-7

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