Human fortilin is a molecular target of dihydroartemisinin

Takayuki Fujita, Kumar Felix, Decha Pinkaew, Nongporn Hutadilok-Towatana, Zhihe Liu, Ken Fujise

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

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 languageEnglish (US)
Pages (from-to)1055-1060
Number of pages6
JournalFEBS Letters
Volume582
Issue number7
DOIs
StatePublished - Apr 2 2008

Keywords

  • DHA
  • Dihydroartemisinin
  • Fortilin

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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