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

Ting Wen Chung, Kok Tong Tan, Hong Lin Chan, Ming Derg Lai, Meng Chi Yen, Yi Ron Li, Sheng Hao Lin, Chi Chen Lin

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10 Citations (Scopus)

Abstract

Interferon-gamma (IFN-γ) has been used to treat various malignant tumors. However, the molecular mechanisms underlying the direct anti-proliferative activity of IFN-γ are poorly understood. In the present study, we examined the in vitro antitumor activity of IFN-γ on two human non-small-cell lung carcinoma (NSCLC) cell lines, H322M and H226. Our findings indicated that IFN-γ 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-γ 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-γ-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-γ. These results provide new mechanistic insights into interferon-γ antitumor activity and further support IFN-γ as a potential therapeutic adjuvant for the treatment of NCSLC.

Original languageEnglish
Pages (from-to)7995-8001
Number of pages7
JournalAsian Pacific Journal of Cancer Prevention
Volume15
Issue number18
DOIs
Publication statusPublished - 2014 Jan 1

All Science Journal Classification (ASJC) codes

  • Epidemiology
  • Oncology
  • Public Health, Environmental and Occupational Health
  • Cancer Research

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