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

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)-gamma in human CRC cells. We found that IFN-gamma increased the expression levels of IDO protein and m RNA in HT29 and SW837 CRC cell lines. Treatment of SW837 cells with EGCG significantly decreased IFN-gamma-induced expression of IDO protein and m RNA 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-gamma was also significantly inhibited by EGCG. Reporter assays indicated that EGCG inhibited the transcriptional activities of IDO promoters, IFN-stimulated response element and IFN-gamma activation sequence, activated by STAT I 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 STAT I activation. EGCG may, thus, serve as a potential agent for antitumor immunotherapy and be useful in the chemoprevention and/or treatment of CRC.