- 作者: Chen-Tzu Kuo; Bing-Chang Chen; Chung-Chi Yu; Chih-Ming Weng; Ming-Jen Hsu; Chien-Chih Chen; Mei-Chieh Chen; Che-Ming Teng; Shiow-Lin Pan; Mauo-Ying Bien; Chung-Hung Shih; Chien-Huang Lin
- 作者服務機構: 1Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan, R.O.C.
- 中文摘要: --
- 英文摘要:
In the present study, we explore the role of apoptosis signal-regulating kinase 1
(ASK1) in denbinobin-induced apoptosis in human lung adenocarcinoma (A549) cells.
Denbinobin-induced cell apoptosis was attenuated by an ASK1 dominant-negative
mutant (ASK1DN), two antioxidants (N-acetyl-L-cysteine (NAC) and glutathione
(GSH)), a c-Jun N-terminal kinase (JNK) inhibitor (SP600125), and an activator
protein-1 (AP-1) inhibitor (curcumin). Treatment of A549 cells with denbinobin
caused increases in ASK1 activity and reactive oxygen species (ROS) production, and
these effects were inhibited by NAC and GSH. Stimulation of A549 cells with
denbinobin caused JNK activation; this effect was markedly inhibited by NAC, GSH,
and ASK1DN. Denbinobin induced c-Jun phosphorylation, the formation of an
AP-1-specific DNA-protein complex, and Bim expression. Bim knockdown using a
bim short interfering RNA strategy also reduced denbinobin-induced A549 cell
apoptosis. The denbinobin-mediated increases in c-Jun phosphorylation and Bim
expression were inhibited by NAC, GSH, SP600125, ASK1DN, JNK1DN, and
JNK2DN. These results suggest that denbinobin might activate ASK1 through ROS
production to cause JNK/AP-1 activation, which in turn induces Bim expression, and
ultimately results in A549 cell apoptosis. - 中文關鍵字: --
- 英文關鍵字: --