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Cancer Chemother Pharmacol. 2011 Feb;67(2):439-46. doi: 10.1007/s00280-010-1344-7. Epub 2010 May 12.

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

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1
Department of Orthopaedic Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.

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.

PMID:
20461381
DOI:
10.1007/s00280-010-1344-7
[Indexed for MEDLINE]
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