Document Detail

Histone deacetylase inhibitor PCI-24781 enhances chemotherapy-induced apoptosis in multidrug-resistant sarcoma cell lines.
MedLine Citation:
PMID:  21508354     Owner:  NLM     Status:  MEDLINE    
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.
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:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Anticancer research     Volume:  31     ISSN:  1791-7530     ISO Abbreviation:  Anticancer Res.     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-04-21     Completed Date:  2011-07-26     Revised Date:  2013-08-20    
Medline Journal Info:
Nlm Unique ID:  8102988     Medline TA:  Anticancer Res     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  1115-23     Citation Subset:  IM    
Department of Orthopaedic Surgery, Huazhong University of Science and Technology, Wuhan 430022, People's Republic of China.
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MeSH Terms
Antineoplastic Agents / 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*
Hydroxamic Acids / pharmacology*
Nuclear Proteins / metabolism
P-Glycoproteins / metabolism
Poly(ADP-ribose) Polymerases / metabolism
Sarcoma / drug therapy*,  pathology*
Grant Support
Reg. No./Substance:
0/Antineoplastic Agents; 0/Benzofurans; 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 Polymerases; EC 3.4.22.-/Caspases; IYO470654U/abexinostat

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