Document Detail


Auranofin induces apoptosis and when combined with retinoic acid enhances differentiation of acute promyelocytic leukaemia cells in vitro.
MedLine Citation:
PMID:  15159275     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
1. Acute promyelocytic leukaemia (APL) is characterized by a block in differentiation at the promyelocyte stage. Here, we describe the effects of auranofin (AF), a coordinated gold compound, on apoptosis and differentiation of APL cells. 2. Nucleosomal DNA fragmentation assay and Hoechst 33342 staining indicated that AF induced apoptosis in APL-derived NB4 cells at low concentrations (0.5-1.0 microm). The AF-induced apoptosis involved caspase-3 activation and specific cleavage of poly-ADP-ribose polymerase. 3. The AF-treated NB4 cells also produced reactive oxygen species (ROS) and cotreatment with N-acetyl-l-cysteine protected the NB4 cells from AF-induced apoptosis. 4. Expression of the CD11b cell surface marker and C/EBPepsilon was increased when the cells were treated for 4 days with 0.3 microm AF and a physiological concentration of all-trans retinoic acid (ATRA, 5 nm). Treatment with AF in combination with ATRA markedly increased the number of cells with differentiated features, such as lobed or multiple nuclei and numerous granules and vacuoles. At these low concentrations, neither AF nor ATRA alone induced significant cell differentiation. 5. These findings suggest not only that AF induces caspase-3-dependent apoptosis via a mechanism involving ROS, but also that the combined treatment with AF and ATRA induces differentiation of NB4 cells. Our results demonstrate a novel characteristic of AF from which an effective drug treatment of APL might be developed.
Authors:
I S Kim; J Y Jin; I H Lee; S J Park
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2004-05-24
Journal Detail:
Title:  British journal of pharmacology     Volume:  142     ISSN:  0007-1188     ISO Abbreviation:  Br. J. Pharmacol.     Publication Date:  2004 Jun 
Date Detail:
Created Date:  2004-06-18     Completed Date:  2005-01-24     Revised Date:  2013-06-09    
Medline Journal Info:
Nlm Unique ID:  7502536     Medline TA:  Br J Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  749-55     Citation Subset:  IM    
Affiliation:
Department of Natural Sciences, College of Medicine, The Catholic University of Korea, Seoul, Korea. ikim@catholic.ac.kr
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MeSH Terms
Descriptor/Qualifier:
Acetylcysteine / pharmacology
Antigens, CD11b / genetics,  metabolism
Antigens, Surface / drug effects,  genetics
Antirheumatic Agents / adverse effects,  antagonists & inhibitors,  chemistry
Apoptosis / drug effects*,  physiology
Auranofin / adverse effects*,  antagonists & inhibitors,  chemistry
Benzimidazoles / diagnostic use
Caspase 3
Caspases / metabolism
Cell Differentiation / drug effects
DNA / chemistry,  drug effects
Drug Therapy, Combination*
Fluorescent Dyes / diagnostic use
HL-60 Cells
Humans
Korea
Leukemia, Promyelocytic, Acute / drug therapy*,  pathology,  physiopathology
Nucleosomes / chemistry,  drug effects
Reactive Oxygen Species / metabolism
Signal Transduction / physiology
Tretinoin / pharmacology,  therapeutic use*
Tumor Cells, Cultured
Chemical
Reg. No./Substance:
0/Antigens, CD11b; 0/Antigens, Surface; 0/Antirheumatic Agents; 0/Benzimidazoles; 0/Fluorescent Dyes; 0/Nucleosomes; 0/Reactive Oxygen Species; 23491-52-3/HOE 33342; 302-79-4/Tretinoin; 34031-32-8/Auranofin; 616-91-1/Acetylcysteine; 9007-49-2/DNA; EC 3.4.22.-/CASP3 protein, human; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases
Comments/Corrections

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