Indoleamine 2,3-Dioxygenase, an Immunomodulatory Protein, Is Suppressed by (-)-Epigallocatechin-3-gallate via Blocking of γ-Interferon-Induced JAK-PKC-δ-STAT1 Signaling in Human Oral Cancer Cells

被引:69
作者
Cheng, Chieh-Wen [1 ]
Shieh, Po-Chuen [2 ,3 ]
Lin, Ying-Chao [1 ,4 ]
Chen, Yi-Jen [5 ]
Lin, Yu-Huei [5 ]
Kuo, Daih-Huang [2 ,3 ]
Liu, Jah-Yao [6 ]
Kao, Jung-Yie [1 ]
Kao, Ming-Ching [5 ]
Way, Tzong-Der [5 ]
机构
[1] Natl Chung Hsing Univ, Coll Life Sci, Inst Biochem, Taichung 40227, Taiwan
[2] Tajen Univ, Coll Pharm & Hlth Care, Dept Pharm, Pingtung, Taiwan
[3] Tajen Univ, Coll Pharm & Hlth Care, Grad Inst Pharmaceut Technol, Pingtung, Taiwan
[4] Buddhist Tzu Chi Gen Hosp, Div Neurosurg, Taichung Branch, Taichung, Taiwan
[5] China Med Univ, Coll Life Sci, Dept Biol Sci & Technol, Taichung, Taiwan
[6] Tri Serv Gen Hosp, Dept Obstet & Gynecol, Taipei, Taiwan
关键词
IDO; EGCG; IFN-gamma; STAT1; human oral cancer; DENDRITIC CELLS; BREAST-CANCER; GREEN TEA; EPIGALLOCATECHIN GALLATE; TRYPTOPHAN CATABOLISM; ADAPTIVE IMMUNITY; IN-VIVO; EXPRESSION; INHIBITION; GENE;
D O I
10.1021/jf903377e
中图分类号
S [农业科学];
学科分类号
082806 [农业信息与电气工程];
摘要
Immune escape is a characteristic of cancer progression, but its underlying molecular mechanism is still poorly understood. An immunomodulatory protein, indoleamide 2,3-dioxygenase (IDO), is induced by gamma-interferon (IFN-gamma) in several immune cells; those cells are observed in cancer cell microenvironment and can enhance immune escape. Previous studies show that IDO is expressed in the process of tumor formation and associated with cancer cell immune tolerance. By locally degrading tryptophan, IDO inhibits the proliferation of T lymphocytes and induces T cell apoptosis, leading to suppression of T cell response. In this study, (-)-epigallocatechin-3-gallate (EGCG), the major constituent of green tea, is found to significantly inhibit the expression of IDO in human oral cancer cell lines. EGCG suppresses the induction of IDO at transcriptional level. Activation of STAT1 is discovered to play an important role in regulating IDO expression by IFN-gamma. The study results demonstrate that EGCG can inhibit translocation of STAT1 into nucleus in IFN-gamma-stimulated human oral cancer cells. In addition, both tyrosine. and serine phosphorylation of STAT1 are to be suppressed by EGCG. Moreover, phosphorylation of PKC-delta, JAK-1, and JAK-2, which are the upstream event for the activation of STAT1, are also inhibited by EGCG in IFN-gamma-stimulated human oral cancer cells. These data show that EGCG inhibited IDO expression by blocking the IFN-gamma-induced JAK-PKC-delta-STAT1 signaling pathway. This study indicates that EGCG is a potential drug for immune and target therapy to enhance cancer therapy by increasing antitumor immunity.
引用
收藏
页码:887 / 894
页数:8
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