| Histone deacetylase inhibitor PCI-24781 enhances chemotherapy-induced apoptosis in multidrug-resistant sarcoma cell lines. | |
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MedLine Citation:
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PMID: 21508354 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The antitumor activity of histone deacetylase inhibitors (HDACI) on multidrug-resistant sarcoma cell lines has not been previously described. Treatment of multidrug-resistant sarcoma cell lines with HDACI PCI-24781 resulted in dose-dependent accumulation of acetylated histone, p21 and poly(ADP-ribose)polymerase (PARP) cleavage products. Growth of these cell lines was inhibited by PCI-24781 at IC(50) of 0.43 to 2.7. When we looked for synergy of PCI-24781 with chemotherapeutic agents, we found that PCI-24781 reverses drug resistance in all four multidrug-resistant sarcoma cell lines and synergizes with chemotherapeutic agents to enhance caspase-3/-7 activity. Expression of RAD51 (a marker for DNA double-strand break repair) was inhibited and the expression of GADD45α (a marker for growth arrest and DNA-damage) was induced by PCI-24781 in multidrug-resistant sarcoma cell lines. In conclusion, HDACI PCI-24781 synergizes with chemotherapeutic drugs to induce apoptosis and reverses drug resistance in multidrug-resistant sarcoma cell lines. |
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Authors:
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Cao Yang; Edwin Choy; Francis J Hornicek; Kirkham B Wood; Joseph H Schwab; Xianzhe Liu; Henry Mankin; Zhenfeng Duan |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Anticancer research Volume: 31 ISSN: 1791-7530 ISO Abbreviation: Anticancer Res. Publication Date: 2011 Apr |
Date Detail:
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Created Date: 2011-04-21 Completed Date: 2011-07-26 Revised Date: 2013-03-06 |
Medline Journal Info:
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Nlm Unique ID: 8102988 Medline TA: Anticancer Res Country: Greece |
Other Details:
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Languages: eng Pagination: 1115-23 Citation Subset: IM |
Affiliation:
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Department of Orthopaedic Surgery, Huazhong University of Science and Technology, Wuhan 430022, People's Republic of China. yangcaom@gmail.com |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Antineoplastic Agents
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pharmacology* Apoptosis / drug effects* Benzofurans / pharmacology* Blotting, Western Caspases / metabolism Cell Cycle Proteins / metabolism Cell Line, Tumor Cell Proliferation / drug effects Drug Resistance, Multiple / drug effects* Drug Resistance, Neoplasm / drug effects* Histone Deacetylase Inhibitors / pharmacology* Humans Hydroxamic Acids / pharmacology* Nuclear Proteins / metabolism P-Glycoproteins / metabolism Poly(ADP-ribose) Polymerases / metabolism Sarcoma / drug therapy*, pathology* |
| Grant Support | |
ID/Acronym/Agency:
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R01-CA119617/CA/NCI NIH HHS; UL1 RR 025758/RR/NCRR NIH HHS; UL1 RR025758/RR/NCRR NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents; 0/Benzofurans; 0/CRA 024781; 0/Cell Cycle Proteins; 0/GADD45A protein, human; 0/Histone Deacetylase Inhibitors; 0/Hydroxamic Acids; 0/Nuclear Proteins; 0/P-Glycoproteins; 0/P-glycoprotein 2; EC 2.4.2.30/Poly(ADP-ribose) Polymerases; EC 3.4.22.-/Caspases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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