Human fortilin is a molecular target of dihydroartemisinin

被引:52
作者
Fujita, Takayuki [1 ]
Felix, Kumar [1 ]
Pinkaew, Decha [1 ,2 ]
Hutadilok-Towatana, Nongporn [2 ]
Liu, Zhihe [1 ]
Fujise, Ken [1 ]
机构
[1] Univ Texas Galveston, Med Branch, Dept Internal Med, Div Cardiol, Galveston, TX 77555 USA
[2] Prince Songkla Univ, Fac Sci, Dept Biochem, Hat Yai 90112, Songkhla, Thailand
关键词
fortilin; dihydroartemisinin; DHA;
D O I
10.1016/j.febslet.2008.02.055
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
Dehydroartemisinin (DHA) is an effective anti-malaria agent. Fortilin is an anti-apoptotic molecule overexpressed in many human cancers. Here, we show that DHA binds human fortilin, increases the ubiquitination of fortilin, shortens fortilin's half-life in a proteasome-dependent fashion, and reduces cellular levels of fortilin in varieties of cells. DHA induced DNA fragmentation in U2OS cells in a fortilin-dependent manner. The fortilin-knocked-down cells were less susceptible-and fortilin-overexpressing cells more susceptible-to DHA than were wild-type cells, suggesting that apoptotic effects of DHA are-at least partly-conferred through fortilin. Together, these data suggest that fortilin is a molecular target of DHA. DHA and its derivative may prove to be viable anti-cancer agents in fortilin-overexpressing cancers. (C) 2008 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码:1055 / 1060
页数:6
相关论文
共 19 条
[1]  
ANSTEY NM, 1993, LANCET, V341, P1035
[2]   REACTION OF ANTIMALARIAL ENDOPEROXIDES WITH SPECIFIC PARASITE PROTEINS [J].
ASAWAMAHASAKDA, W ;
ITTARAT, I ;
PU, YM ;
ZIFFER, H ;
MESHNICK, SR .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1994, 38 (08) :1854-1858
[3]   Molecular cloning and expression of a mammalian homologue of a translationally controlled tumor protein (TCTP) gene from Penaeus monodon shrimp [J].
Bangrak, P ;
Graidist, P ;
Chotigeat, W ;
Phongdara, A .
JOURNAL OF BIOTECHNOLOGY, 2004, 108 (03) :219-226
[4]   The Plasmodium falciparum translationally controlled tumor protein homolog and its reaction with the antimalarial drug artemisinin [J].
Bhisutthibhan, J ;
Pan, XQ ;
Hossler, PA ;
Walker, DJ ;
Yowell, CA ;
Carlton, J ;
Dame, JB ;
Meshnick, SR .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (26) :16192-16198
[5]   Immunoprecipitation of [3H]dihydroartemisinin translationally controlled tumor protein (TCTP) adducts from Plasmodium falciparum-infected erythrocytes by using anti-TCTP antibodies [J].
Bhisutthibhan, J ;
Meshnick, SR .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2001, 45 (08) :2397-2399
[6]  
China Cooperative Research Group on Qinghaosu and its Derivatives as Antimalarials, 1982, J TRADIT CHIN MED, V2, P3
[7]   Biosensor analysis of the interaction between immobilized human serum albumin and drug compounds for prediction of human serum albumin binding levels [J].
Frostell-Karlsson, Å ;
Remaeus, A ;
Roos, H ;
Andersson, K ;
Borg, P ;
Hämäläinen, M ;
Karlsson, R .
JOURNAL OF MEDICINAL CHEMISTRY, 2000, 43 (10) :1986-1992
[8]   Communication - Preferential interaction of sentrin with a ubiquitin-conjugating enzyme, Ubc9 [J].
Gong, LM ;
Kamitani, T ;
Fujise, K ;
Caskey, LS ;
Yeh, ETH .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (45) :28198-28201
[9]   Antiapoptotic protein partners fortilin and MCL1 independently protect cells from 5-fluorouracil-induced cytotoxicity [J].
Graidist, P ;
Phongdara, A ;
Fujise, K .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (39) :40868-40875
[10]   Dihydroartemisinin enhances radiosensitivity of human glioma cells in vitro [J].
Kim, SJ ;
Kim, MS ;
Lee, JW ;
Lee, CH ;
Yoo, H ;
Shin, SH ;
Park, MJ ;
Lee, SH .
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY, 2006, 132 (02) :129-135