title: 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.
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.
authors.affiliation: Division of Chest Medicine, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan E-mail : lincc@dragon.nchu.edu.tw.
authors.forename: Ting Wen
authors.initials: TW
authors.lastname: Chung
authors.forename: Kok-Tong
authors.initials: KT
authors.lastname: Tan
authors.forename: Hong-Lin
authors.initials: HL
authors.lastname: Chan
authors.forename: Ming-Derg
authors.initials: MD
authors.lastname: Lai
authors.forename: Meng-Chi
authors.initials: MC
authors.lastname: Yen
authors.forename: Yi-Ron
authors.initials: YR
authors.lastname: Li
authors.forename: Sheng Hao
authors.initials: SH
authors.lastname: Lin
authors.forename: Chi-Chen
authors.initials: CC
authors.lastname: Lin
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D000998:Antiviral Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism*; D007371:Interferon-gamma / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D000998:Antiviral Agents; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D007371:Interferon-gamma; D045304:Cytochromes c