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Tryptamine and dimethyltryptamine inhibit indoleamine 2,3 dioxygenase and increase the tumor‐reactive effect of peripheral blood mononuclear cells
Author(s) -
Tourino Melissa Cavalheiro,
Oliveira Edson Mendes,
Bellé Luziane Potrich,
Knebel Franciele Hinterholz,
Albuquerque Renata Chaves,
Dörr Felipe Augusto,
Okada Sabrina Sayori,
Migliorini Silene,
Soares Irene Silva,
Campa Ana
Publication year - 2013
Publication title -
cell biochemistry and function
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.933
H-Index - 61
eISSN - 1099-0844
pISSN - 0263-6484
DOI - 10.1002/cbf.2980
Subject(s) - indoleamine 2,3 dioxygenase , tryptamine , kynurenine , peripheral blood mononuclear cell , serotonin , chemistry , pharmacology , kynurenine pathway , tryptophan , immune system , serotonergic , in vitro , immunology , biochemistry , biology , receptor , amino acid
Indoleamine 2,3‐dioxygenase (IDO) is an interferon‐γ (IFN‐γ)–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 μM, respectively. This inhibitory effect was also observed on constitutively expressed or IFN‐γ–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 © 2013 John Wiley & Sons, Ltd.