Abstract
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.
Original language | English (US) |
---|---|
Pages (from-to) | 1055-1060 |
Number of pages | 6 |
Journal | FEBS Letters |
Volume | 582 |
Issue number | 7 |
DOIs | |
State | Published - Apr 2 2008 |
Externally published | Yes |
Keywords
- DHA
- Dihydroartemisinin
- Fortilin
ASJC Scopus subject areas
- Biophysics
- Structural Biology
- Biochemistry
- Molecular Biology
- Genetics
- Cell Biology