(-)-Epigallocatechin gallate inhibits the expression of indoleamine 2,3-dioxygenase in human colorectal cancer cells

Ogawa,Kengo; Hara,Takeshi; Shimizu,Masahito; Nagano,Junji; Ohno,Tomohiko; Hoshi,Masato; Ito,Hiroyasu; Tsurumi,Hisashi; Saito,Kuniaki; Seishima,Mitsuru; Moriwaki,Hisataka

doi:10.3892/ol.2012.761

(-)-Epigallocatechin gallate inhibits the expression of indoleamine 2,3-dioxygenase in human colorectal cancer cells

Authors:
- Kengo Ogawa
- Takeshi Hara
- Masahito Shimizu
- Junji Nagano
- Tomohiko Ohno
- Masato Hoshi
- Hiroyasu Ito
- Hisashi Tsurumi
- Kuniaki Saito
- Mitsuru Seishima
- Hisataka Moriwaki
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Affiliations: Department of Internal Medicine, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan , Department of Informative Clinical Medicine, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan , Human Health Sciences, Graduate School of Medicine and Faculty of Medicine, Kyoto University, Kyoto 606-8501, Japan
Published online on: June 15, 2012 https://doi.org/10.3892/ol.2012.761
Pages: 546-550

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Abstract

Immune escape, the ability of tumor cells to avoid tumor-specific immune responses, occurs during the development and progression of several types of human malignancies, including colorectal cancer (CRC). Indoleamine 2,3‑dioxygenase (IDO), the tryptophan catabolic enzyme, plays a significant role in regulating the immune response and provides tumor cells with a potent tool to evade the immune system. In the present study, we examined the effects of (-)‑epigallocatechin gallate (EGCG), the major catechin in green tea, on the inhibition of IDO expression induced by interferon (IFN)-γ in human CRC cells. We found that IFN-γ increased the expression levels of IDO protein and mRNA in HT29 and SW837 CRC cell lines. Treatment of SW837 cells with EGCG significantly decreased IFN‑γ‑induced expression of IDO protein and mRNA in a dose‑dependent manner. Enzymatic activity of IDO, determined by the concentration of L‑kynurenine in the culture medium, was also significantly inhibited by EGCG treatment. Phosphorylation of signal transducer and activator of transcription 1 (STAT1) induced by IFN-γ was also significantly inhibited by EGCG. Reporter assays indicated that EGCG inhibited the transcriptional activities of IDO promoters, IFN‑stimulated response element and IFN-γ activation sequence, activated by STAT1 phosphorylation. These findings suggest that EGCG may exert antitumor effects on CRC, at least in part, by inhibiting the expression and function of IDO through the suppression of STAT1 activation. EGCG may, thus, serve as a potential agent for antitumor immunotherapy and be useful in the chemoprevention and/or treatment of CRC.

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