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Immunosuppressant PG490 (triptolide) induces apoptosis through the activation of caspase-3 and down-regulation of XIAP in U937 cells

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Author(s)
박종욱권택규서성일
Alternative Author(s)
Park, Jong WookKwon, Taeg KyuSuh, Seong Il
Publication Year
2003
Abstract
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.

Keywords
Triptolide;
Apoptosis;
U937;
XIAP;
Caspase
Department
Dept. of Immunology (면역학)
Dept. of Microbiology (미생물학)
Publisher
School of Medicine
Citation
Biochemical Pharmacology, Vol.66(2) : 273-280, 2003
Type
Article
ISSN
0006-2952
DOI
10.1016/S0006-2952(03)00282-X
URI
http://kumel.medlib.dsmc.or.kr/handle/2015.oak/35187
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