The JNK inhibitor SP600125 enhances dihydroartemisinin-induced apoptosis by accelerating Bax translocation into mitochondria in human lung adenocarcinoma cells

被引：45

作者：

Lu, Ying-Ying ^{[1
,2
]}

Chen, Tong-Sheng ^{[1
,2
]}

Wang, Xiao-Ping ^{[3
]}

Qu, Jun-Le ^{[4
]}

Chen, Min ^{[1
,2
]}

机构：

[1] S China Normal Univ, MOE Key Lab Laser Life Sci, Guangzhou 510631, Guangdong, Peoples R China

[2] S China Normal Univ, Inst Laser Life Sci, Guangzhou 510631, Guangdong, Peoples R China

[3] Jinan Univ, Dept Anesthesiol, Affiliated Hosp 1, Guangzhou 510632, Guangdong, Peoples R China

[4] Shenzhen Univ, Inst Optoelect, Key Lab Optoelect Devices & Syst, Minist Educ & Guangdong Prov, Shenzhen 518060, Peoples R China

来源：

FEBS LETTERS | 2010年 / 584卷 / 18期

关键词：

SP600125; Dihydroartemisinin; Apoptosis; Bax; Fluorescence recovery after photobleaching; IN-VITRO; ARTEMISININ; PROTEIN; PHOSPHORYLATION; DERIVATIVES; ACTIVATION; HEPATOMA;

D O I：

10.1016/j.febslet.2010.08.014

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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. (c) 2010 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

引用

页码：4019 / 4026

页数：8

共 21 条

[1] ROS, stress-activated kinases and stress signaling in cancer [J].

Benhar, M ;

Engelberg, D ;

Levitzki, A .

EMBO REPORTS, 2002, 3 (05) :420-425

[2] SP600125, an anthrapyrazolone inhibitor of Jun N-terminal kinase [J].

Bennett, BL ;

Sasaki, DT ;

Murray, BW ;

O'Leary, EC ;

Sakata, ST ;

Xu, WM ;

Leisten, JC ;

Motiwala, A ;

Pierce, S ;

Satoh, Y ;

Bhagwat, SS ;

Manning, AM ;

Anderson, DW .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (24) :13681-13686

[3] Dihydroartemisinin induces apoptosis and sensitizes human ovarian cancer cells to carboplatin therapy [J].

Chen, Tao ;

Li, Mian ;

Zhang, Ruiwen ;

Wang, Hui .

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, 2009, 13 (07) :1358-1370

[4] JNK signaling in apoptosis [J].

Dhanasekaran, D. N. ;

Reddy, E. P. .

ONCOGENE, 2008, 27 (48) :6245-6251

[5] Dihydroartemisinin is cytotoxic to papillomavirus-expressing epithelial cells in vitro and in vivo [J].

Disbrow, GL ;

Baege, AC ;

Kierpiec, KA ;

Yuan, H ;

Centeno, JA ;

Thibodeaux, CA ;

Hartmann, D ;

Schlegel, R .

CANCER RESEARCH, 2005, 65 (23) :10854-10861

[6] MCL-1 inhibits BAX in the absence of MCL-1/BAX interaction [J].

Germain, Marc ;

Milburn, Jocelyn ;

Duronio, Vincent .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2008, 283 (10) :6384-6392

[7] Artemisinin and derivatives: the future for malaria treatment? [J].

Haynes, RK .

CURRENT OPINION IN INFECTIOUS DISEASES, 2001, 14 (06) :719-726

[8] Experimental therapy of hepatoma with artemisinin and its derivatives:: In vitro and in vivo activity, chemosensitization, and mechanisms of action [J].

Hou, Junmei ;

Wang, Disong ;

Zhang, Ruiwen ;

Wang, Hui .

CLINICAL CANCER RESEARCH, 2008, 14 (17) :5519-5530

[9] Required roles of Bax and JNKs in central and peripheral nervous system death of retinoblastoma-deficient mice [J].

Keramaris, Elizabeth ;

Ruzhynsky, Vladamir A. ;

Callaghan, Steve M. ;

Wong, Estelle ;

Davis, Roger J. ;

Flavell, Richard ;

Slack, Ruth S. ;

Park, David S. .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2008, 283 (01) :405-415

[10] JNK- and p38 kinase-mediated phosphorylation of Bax leads to its activation and mitochondrial translocation and to apoptosis of human hepatoma HepG2 cells [J].

Kim, Bong-Jo ;

Ryu, Seung-Wook ;

Song, Byoung-Joon .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2006, 281 (30) :21256-21265

← 1 2 3 →