Human fortilin is a molecular target of dihydroartemisinin

  • Fujita T
  • Felix K
  • Pinkaew D
 et al. 
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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. © 2008 Federation of European Biochemical Societies.

Author-supplied keywords

  • DHA
  • Dihydroartemisinin
  • Fortilin

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