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Caspase-8 acts as a key upstream executor of mitochondria during justicidin A-induced apoptosis in human hepatoma cells
Authors:Su Chun-Li  Huang Lynn L H  Huang Li-Min  Lee Jenq-Chang  Lin Chun-Nan  Won Shen-Jeu
Institution:Department of Nursing, Chang Jung Christian University, Tainan 711, Taiwan.
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 (Delta psi(m)), and caused the release of cytochrome c and Smac/DIABLO in Hep 3B and Hep G2 cells. Justicidin A also reduced Bcl-x(L) and increased Bax and Bak in mitochondria. Caspase-8 inhibitor (Z-IETD) attenuated the justicidin A-induced disruption of Delta psi(m). 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.
Keywords:HCC  hepatocellular carcinoma  PBMC  peripheral blood mononuclear cells  Smac/DIABLO  second mitochondria-derived activator of caspase/direct IAP binding protein with low pI  PARP  poly(ADP-ribose) polymerase  DFF  DNA fragmentation factor  Δψm  mitochondrial membrane potential  XIAP  X-linked apoptosis-inhibiting protein  MTT  3-(4  5-dimethylthiazol-2-yl)-2  5-diphenyltetrazolium bromide  mAB  monoclonal antibody  pAB  polyclonal antibody
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