Formosanin C-induced apoptosis requires activation of caspase-2 and change of mitochondrial membrane potential

Jenq Chang Lee, Chun Li Su, Lin Lin Chen, Shen Jeu Won

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Formosanin C is a pure compound isolated from Paris formosana Hayata (Liliaceae). The antitumor efficacy of formosanin C has been observed in cultured cells and animal systems. However, the molecular mechanisms of formosanin C remain unknown. The results of the present study indicate that formosanin C induced apoptosis of HT-29 cells characterized by exposure of phosphatidylserine, accumulation of cells at the sub-G1 phase, fragmentation of DNA, and change of nuclear morphology in a time- and dose-related manner. The apoptotic signaling cascades may proceed via proteolytic activation of caspase-2, change of mitochondrial membrane potential (Δεm), release of cytochrome c and second mitochondria-derived activator of caspase/direct IAP binding protein with low pI (Smac/DIABLO), activation of caspase-9 and -3, and cleavage of poly(ADP-ribose) polymerase (PARP). Increase in apoptosis-inducing factor and endonuclease G expressions in nuclei, and increase in Bax and Bak expressions and decrease in Bcl-XL expression on mitochondria were also observed in formosanin C-treated HT-29 cells. Attenuation of formosanin C-induced change of Δεm by caspase-2 inhibitor (Z-VDVAC) implies that caspase-2 acts upstream of the mitochondria. Blockage of formosanin C-induced apoptotic process by using either permeability transition pore inhibitor (cyclosporine A) or caspase-9 inhibitor (Z-LEHD) demonstrates the necessity of mitochondria and caspase-9 in formosanin C-induced apoptosis of HT-29 cells. Taken together, the apoptotic mechanism of formosanin C in human colorectal cancer HT-29 cells involves activation of caspase-2 and the dysfunction of mitochondria.

Original languageEnglish
Pages (from-to)503-513
Number of pages11
JournalCancer Science
Volume100
Issue number3
DOIs
Publication statusPublished - 2009 Apr 30

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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