title: (-)-Epigallocatechin gallate inhibits the expression of indoleamine 2,3-dioxygenase in human colorectal cancer cells.
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.
authors.affiliation: Department of Internal Medicine, Gifu University Graduate School of Medicine, Gifu 501-1194.
authors.forename: Kengo
authors.initials: K
authors.lastname: Ogawa
authors.forename: Takeshi
authors.initials: T
authors.lastname: Hara
authors.forename: Masahito
authors.initials: M
authors.lastname: Shimizu
authors.forename: Junji
authors.initials: J
authors.lastname: Nagano
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Ohno
authors.forename: Masato
authors.initials: M
authors.lastname: Hoshi
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Ito
authors.forename: Hisashi
authors.initials: H
authors.lastname: Tsurumi
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Saito
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Seishima
authors.forename: Hisataka
authors.initials: H
authors.lastname: Moriwaki
keywords: (-)-epigallocatechin gallate; 3-dioxygenase; colorectal cancer cells; indoleamine 2; interferon-γ; signal transducer and activator of transcription 1