The JNK inhibitor SP600125 enhances dihydroartemisinin-induced apoptosis by accelerating Bax translocation into mitochondria in human lung adenocarcinoma cells.
The C-Jun N-terminal Kinase (JNK) inhibitor SP600125 is widely used to inhibit the JNK-mediated Bax activation and cell apoptosis. However, this report demonstrates that SP600125 synergistically enhances the dihydroartemisinin (DHA)-induced human lung adenocarcinoma cell apoptosis by accelerating Bax translocation and subsequent intrinsic apoptotic pathway involving mitochondrial membrane depolarization, cytochrome c release, caspase-9 and caspase-3 activation. The dynamical analysis of GFP-Bax mobility inside single living cells using fluorescence recovery after photobleaching revealed that SP600125 aggravated the DHA-induced decrease of Bax mobility and Bax translocation. These results for the first time present a novel pro-apoptotic action of SP600125 in DHA-induced apoptosis.
Lu
Ying-Ying
YY
MOE Key Laboratory of Laser Life Science and Institute of Laser Life Science, South China Normal University, Guangzhou, China.
Chen
Tong-Sheng
TS
Wang
Xiao-Ping
XP
Qu
Jun-Le
JL
Chen
Min
M
D000873:Anthracenes / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D037621:Artemisinins / Q000494:pharmacology; D045744:Cell Line, Tumor; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*; D008928:Mitochondria / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D021381:Protein Transport / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000378:metabolism*
D000873:Anthracenes; D037621:Artemisinins; D047428:Protein Kinase Inhibitors; D051028:bcl-2-Associated X Protein; C432165:pyrazolanthrone; C039060:artenimol; D048031:JNK Mitogen-Activated Protein Kinases