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

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

Research output: Contribution to journalArticle

25 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)546-550
Number of pages5
JournalOncology Letters
Volume4
Issue number3
DOIs
Publication statusPublished - 01-09-2012
Externally publishedYes

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Indoleamine-Pyrrole 2,3,-Dioxygenase
Colorectal Neoplasms
Interferons
STAT1 Transcription Factor
Phosphorylation
Tumor Escape
Kynurenine
Neoplasms
Messenger RNA
Catechin
Chemoprevention
Response Elements
Tea
epigallocatechin gallate
Tryptophan
Antineoplastic Agents
Immunotherapy
Transcriptional Activation
Culture Media
Immune System

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Ogawa, Kengo ; Hara, Takeshi ; Shimizu, Masahito ; Nagano, Junji ; Ohno, Tomohiko ; Hoshi, Masato ; Ito, Hiroyasu ; Tsurumi, Hisashi ; Saito, Kuniaki ; Seishima, Mitsuru ; Moriwaki, Hisataka. / (-)-Epigallocatechin gallate inhibits the expression of indoleamine 2,3-dioxygenase in human colorectal cancer cells. In: Oncology Letters. 2012 ; Vol. 4, No. 3. pp. 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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Ogawa, K, Hara, T, Shimizu, M, Nagano, J, Ohno, T, Hoshi, M, Ito, H, Tsurumi, H, Saito, K, Seishima, M & Moriwaki, H 2012, '(-)-Epigallocatechin gallate inhibits the expression of indoleamine 2,3-dioxygenase in human colorectal cancer cells', Oncology Letters, vol. 4, no. 3, pp. 546-550. https://doi.org/10.3892/ol.2012.761

(-)-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.

In: Oncology Letters, Vol. 4, No. 3, 01.09.2012, p. 546-550.

Research output: Contribution to journalArticle

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T1 - (-)-Epigallocatechin gallate inhibits the expression of indoleamine 2,3-dioxygenase in human colorectal cancer cells

AU - Ogawa, Kengo

AU - Hara, Takeshi

AU - Shimizu, Masahito

AU - Nagano, Junji

AU - Ohno, Tomohiko

AU - Hoshi, Masato

AU - Ito, Hiroyasu

AU - Tsurumi, Hisashi

AU - Saito, Kuniaki

AU - Seishima, Mitsuru

AU - Moriwaki, Hisataka

PY - 2012/9/1

Y1 - 2012/9/1

N2 - 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.

AB - 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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