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Histone deacetylase inhibitor (HDACI) PCI24781 potentiates cytotoxic effects of doxorubicin in bone sarcoma cells

Histone deacetylase inhibitor (HDACI) PCI24781 potentiates cytotoxic effects of doxorubicin in bone sarcoma cells,10.1007/s00280-010-1344-7,Cancer Che

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Histone deacetylase inhibitor (HDACI) PCI24781 potentiates cytotoxic effects of doxorubicin in bone sarcoma cells   (Citations: 1)
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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.
Journal: Cancer Chemotherapy and Pharmacology - CANCER CHEMOTHER PHARMACOL , vol. 67, no. 2, pp. 439-446, 2011
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