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IFN-γinduces cell death in human hepatoma cells through a trail/death receptor-mediated apoptotic pathway

 Eui-Cheol Shin  ;  Ju Mi Ahn  ;  Chul Hoon Kim  ;  Youjeong Choi  ;  Young Soo Ahn  ;  Hoguen Kim  ;  Se Jong Kim  ;  Jeon Han Park 
 INTERNATIONAL JOURNAL OF CANCER, Vol.93(2) : 262-268, 2001 
Journal Title
Issue Date
Apoptosis* ; Apoptosis Regulatory Proteins ; Carcinoma, Hepatocellular/pathology ; Caspase 1/genetics ; Caspase 1/metabolism ; Caspase 3 ; Caspases/metabolism ; Cell Survival/drug effects ; Enzyme Activation ; Fas Ligand Protein ; Humans ; Immunoglobulin Fc Fragments/genetics ; Interferon-gamma/pharmacology* ; Liver Neoplasms/pathology ; Membrane Glycoproteins/genetics ; Membrane Glycoproteins/metabolism* ; RNA, Messenger/metabolism ; Receptors, TNF-Related Apoptosis-Inducing Ligand ; Receptors, Tumor Necrosis Factor/genetics ; Receptors, Tumor Necrosis Factor/metabolism* ; Recombinant Proteins/pharmacology ; TNF-Related Apoptosis-Inducing Ligand ; Tumor Cells, Cultured ; Tumor Necrosis Factor-alpha/genetics ; Tumor Necrosis Factor-alpha/metabolism* ; fas Receptor/genetics ; fas Receptor/metabolism
IFN-γ ; hepatoma ; TRAIL ; apoptosis ; death receptor
We demonstrated the induction of cell death in a hepatoma cell line by IFN-gamma and its possible mechanism. Among the 2 hepatitis B virus (HBV)-associated hepatoma cell lines, SNU-354 and SNU-368, IFN-gamma induced cell death and increased caspase-3 activity in SNU-368 but not in SNU-354. IFN-gamma induced several changes in the mRNA expression level of apoptosis-regulating genes, e.g., increased expression of Fas, caspase-1 and TNF-related apoptosis-inducing ligand (TRAIL). In particular, IFN-gamma potently increased the mRNA expression of TRAIL in both cell lines. However, it did not change the mRNA expression level of death-mediating TRAIL receptors, e.g., DR4 and DR5, which were constitutively expressed in both cell lines. In contrast, the decoy receptor DcR1 was expressed in SNU-354 but not in SNU-368, and its expression level in SNU-354 was increased by IFN-gamma. Another decoy receptor, DcR2, was constitutively expressed in both cell lines; however, its expression level in SNU-368 was decreased by IFN-gamma. In addition, exogenous recombinant TRAIL reduced viability in SNU-368, but not in SNU-354, cells. From these findings, we speculated that TRAIL up-regulation and the subsequent TRAIL-mediated apoptosis serve as a mechanism of IFN-gamma-induced cell death in SNU-368. To confirm this hypothesis, we demonstrated that soluble DR4-Fc fusion protein, a TRAIL pathway inhibitor, inhibited IFN-gamma-induced cell death in SNU-368. Our results demonstrated that IFN-gamma acts as an inducer of cell death through TRAIL-mediated apoptosis.
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1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers
Yonsei Authors
Kim, Se Jong(김세종)
Kim, Chul Hoon(김철훈) ORCID logo https://orcid.org/0000-0002-7360-429X
Kim, Hogeun(김호근)
Park, Jeon Han(박전한) ORCID logo https://orcid.org/0000-0001-9604-3205
Ahn, Young Soo(안영수)
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