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Human fortilin is a molecular target of dihydroartemisinin
Author(s) -
Fujita Takayuki,
Felix Kumar,
Pinkaew Decha,
Hutadilok-Towataongporn,
Liu Zhihe,
Fujise Ken
Publication year - 2008
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2008.02.055
Subject(s) - dihydroartemisinin , apoptosis , dna fragmentation , cancer cell , fragmentation (computing) , ubiquitin , biology , microbiology and biotechnology , chemistry , biochemistry , cancer research , cancer , gene , programmed cell death , genetics , plasmodium falciparum , malaria , immunology , artemisinin , ecology
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.