Immunosuppressant PG490 (triptolide) induces apoptosis through the activation of caspase-3 and down-regulation of XIAP in U937 cells.
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.
Choi
Yun-Jung
YJ
Department of Immunology, School of Medicine, Keimyung University, 194 DongSan-Dong Jung-Gu, Taegu 700-712, South Korea.
Kim
Tae Gyu
TG
Kim
Young-Ho
YH
Lee
Sung-Hee
SH
Kwon
Young Kyu
YK
Suh
Seong-Il
SI
Park
Jong-Wook
JW
Kwon
Taeg Kyu
TK
D017209:Apoptosis; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D004224:Diterpenes / Q000494:pharmacology*; D015536:Down-Regulation; D004789:Enzyme Activation; D004852:Epoxy Compounds; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D009363:Neoplasm Proteins / Q000378:metabolism; D010616:Phenanthrenes; D011506:Proteins / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D020298:U937 Cells; D051636:X-Linked Inhibitor of Apoptosis Protein
D004224:Diterpenes; D004852:Epoxy Compounds; D007166:Immunosuppressive Agents; D009363:Neoplasm Proteins; D010616:Phenanthrenes; D011506:Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; C030193:immunosuppressive acidic protein; C001899:triptolide; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases