Caspase-8 acts as a key upstream executor of mitochondria during justicidin A-induced apoptosis in human hepatoma cells

Chun Li Su, Lynn L.H. Huang, Li Min Huang, Jenq Chang Lee, Chun Nan Lin, Shen Jeu Won

Research output: Contribution to journalArticlepeer-review

36 Citations (Scopus)

Abstract

Justicia procumbens is a traditional Taiwanese herbal remedy used to treat fever, pain, and cancer. Justicidin A, isolated from Justicia procumbens, has been reported to suppress in vitro growth of several tumor cell lines as well as hepatoma cells. In this study, justicidin A activated caspase-8 to increase tBid, disrupted mitochondrial membrane potential (Δψm), and caused the release of cytochrome c and Smac/DIABLO in Hep 3B and Hep G2 cells. Justicidin A also reduced Bcl-xL and increased Bax and Bak in mitochondria. Caspase-8 inhibitor (Z-IETD) attenuated the justicidin A-induced disruption of Δψm. Growth of Hep 3B implanted in NOD-SCID mice was suppressed significantly by oral justicidin A (20 mg/kg/day). These results indicate that justicidin A-induced apoptosis in these cells proceeds via caspase-8 and is followed by mitochondrial disruption. Supplementary materials are available at http://myweb.ncku.edu.tw/~a725/.

Original languageEnglish
Pages (from-to)3185-3191
Number of pages7
JournalFEBS Letters
Volume580
Issue number13
DOIs
Publication statusPublished - 2006 May 29

Keywords

  • Apoptosis
  • Caspase
  • Hepatoma
  • Justicidin A
  • Mitochondria
  • Tumor growth

ASJC Scopus subject areas

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

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