期刊
CELL BIOCHEMISTRY AND FUNCTION
卷 31, 期 5, 页码 361-364出版社
WILEY
DOI: 10.1002/cbf.2980
关键词
immune escape; kynurenine pathway; tolerance; tryptophan metabolism; tumor growth
资金
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo [2009/14632-3]
Indoleamine 2,3-dioxygenase (IDO) is an interferon- (IFN-)-induced tryptophan-degrading enzyme, producing kynurenine (KYN) that participates in the mechanism of tumor immune tolerance. Thus, IDO inhibition has been considered a strategy for anticancer therapy. The aim of this study was to identify whether the metabolites originated from the competitive routes of tryptophan metabolism, such as the serotonergic or N, N-dimethyltryptamine (DMT) pathways, have inhibitory effects on recombinant human IDO (rhIDO) activity. Serotonin and melatonin had no effect; on the other hand, tryptamine (TRY) and DMT modulated the activity of rhIDO as classical non-competitive inhibitors, with Ki values of 156 and 506 M, respectively. This inhibitory effect was also observed on constitutively expressed or IFN--induced IDO in the A172 human glioma cell line. TRY and DMT increased the cytotoxic activity of peripheral blood mononuclear cells (PBMCs) in co-culture assays. We conclude that the IDO inhibition by TRY and DMT contributed to a more effective tumor-reactive response by the PBMCs. Copyright (c) 2013 John Wiley & Sons, Ltd.
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