Document Detail


Immunosuppressant PG490 (triptolide) induces apoptosis through the activation of caspase-3 and down-regulation of XIAP in U937 cells.
MedLine Citation:
PMID:  12826269     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PG490 (triptolide) is a natural, biologically active compound extracted from Chinese herb Tripterygium wilfordii. It possesses potent anti-inflammatory and immunosuppressive properties. The mechanism by which triptolide initiates apoptosis remains poorly understood. In the present report, we investigated the effect of triptolide on the apoptotic pathway in U937 human promonocytic cells. We show that triptolide inhibits U937 cells growth by inducing apoptosis. Following treatment of U937 cells with 25 nM triptoride for 24 hr, morphological features of apoptosis and DNA fragmentation were observed. Caspase inhibitors significantly reduced triptolide-induced caspase-3 activation. In addition, apoptosis triggered by triptolide was not associated with the generation of reactive oxygen species, which was not affected by the antioxidant N-acetylcysteine (NAC). The data collectively indicate that the cytotoxic effect of triptolide in U937 cells is attributable to apoptosis mediated by the caspase-3 activation pathway that may be associated with XIAP down-regulation.
Authors:
Yun-Jung Choi; Tae Gyu Kim; Young-Ho Kim; Sung-Hee Lee; Young Kyu Kwon; Seong-Il Suh; Jong-Wook Park; Taeg Kyu Kwon
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biochemical pharmacology     Volume:  66     ISSN:  0006-2952     ISO Abbreviation:  Biochem. Pharmacol.     Publication Date:  2003 Jul 
Date Detail:
Created Date:  2003-06-26     Completed Date:  2003-07-30     Revised Date:  2008-05-14    
Medline Journal Info:
Nlm Unique ID:  0101032     Medline TA:  Biochem Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  273-80     Citation Subset:  IM    
Affiliation:
Department of Immunology, School of Medicine, Keimyung University, 194 DongSan-Dong Jung-Gu, Taegu 700-712, South Korea.
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MeSH Terms
Descriptor/Qualifier:
Apoptosis*
Caspase 3
Caspases / metabolism*
Diterpenes / pharmacology*
Down-Regulation
Enzyme Activation
Epoxy Compounds
Humans
Immunosuppressive Agents / pharmacology*
Neoplasm Proteins / metabolism
Phenanthrenes*
Proteins / metabolism*
Proto-Oncogene Proteins c-bcl-2 / metabolism
U937 Cells
X-Linked Inhibitor of Apoptosis Protein
Chemical
Reg. No./Substance:
0/Diterpenes; 0/Epoxy Compounds; 0/Immunosuppressive Agents; 0/Neoplasm Proteins; 0/Phenanthrenes; 0/Proteins; 0/Proto-Oncogene Proteins c-bcl-2; 0/X-Linked Inhibitor of Apoptosis Protein; 0/XIAP protein, human; 0/immunosuppressive acidic protein; 38748-32-2/triptolide; EC 3.4.22.-/CASP3 protein, human; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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