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

doi:10.7314/apjcp.2014.15.18.7995

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.

Highlights

Lung cancer is the most common cancer in terms of both incidence and mortality worldwide
Our findings indicated that IFN-γ treatment caused a time-dependent reduction in cell viability and induced apoptosis through a FasAssociated Death Domain (FADD)-mediated caspase-8/tBid/mitochondria-dependent pathway in both cell lines
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-non-small-cell lung carcinoma (NSCLC) cancer effect of IFN-γ

Summary

Introduction

Lung cancer is the most common cancer in terms of both incidence and mortality worldwide. Mechanisms of Interferon Gamma-induced Apoptosis in Human Non-small Cell Lung Cancer 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

Results

Conclusion