Induction of Indoleamine 2,3-dioxygenase (IDO) Enzymatic Activity Contributes to Interferon-Gamma Induced Apoptosis and Death Receptor 5 Expression in Human Non-small Cell Lung Cancer Cells

  • Chung, Ting Wen (Division of Chest Medicine, Department of Internal Medicine, Changhua Christian Hospital) ;
  • Tan, Kok-Tong (Tungs' Taichung MetroHarbor Hospital) ;
  • Chan, Hong-Lin (Institute of Bioinformatics and Structural Biology and Department of Medical Sciences, National Tsing Hua University) ;
  • Lai, Ming-Derg (Department of Biochemistry and Molecular Biology, National Cheng-Kung University) ;
  • Yen, Meng-Chi (Department of Biochemistry and Molecular Biology, National Cheng-Kung University) ;
  • Li, Yi-Ron (Institute of Biomedical Sciences, College of Life Science, National Chung Hsing University) ;
  • Lin, Sheng Hao (Division of Chest Medicine, Department of Internal Medicine, Changhua Christian Hospital) ;
  • Lin, Chi-Chen (Division of Chest Medicine, Department of Internal Medicine, Changhua Christian Hospital)
  • 발행 : 2014.10.11


Interferon-gamma (IFN-${\gamma}$) has been used to treat various malignant tumors. However, the molecular mechanisms underlying the direct anti-proliferative activity of IFN-${\gamma}$ are poorly understood. In the present study, we examined the in vitro antitumor activity of IFN-${\gamma}$ on two human non-small-cell lung carcinoma (NSCLC) cell lines, H322M and H226. Our findings indicated that IFN-${\gamma}$ treatment caused a time-dependent reduction in cell viability and induced apoptosis through a FADD-mediated caspase-8/tBid/mitochondria-dependent pathway in both cell lines. Notably, we also postulated that IFN-${\gamma}$ increased indoleamine 2,3-dioxygenase (IDO) expression and enzymatic activity in H322M and H226 cells. In addition, inhibition of IDO activity by the IDO inhibitor 1-MT or tryptophan significantly reduced IFN-${\gamma}$-induced apoptosis and death receptor 5 (DR5) expression, which suggests that IDO enzymatic activity plays an important role in the anti-NSCLC cancer effect of IFN-${\gamma}$. These results provide new mechanistic insights into interferon-${\gamma}$ antitumor activity and further support IFN-${\gamma}$ as a potential therapeutic adjuvant for the treatment of NCSLC.


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