title: Tryptamine and dimethyltryptamine inhibit indoleamine 2,3 dioxygenase and increase the tumor-reactive effect of peripheral blood mononuclear cells.
abstract: 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.
authors.affiliation: Department of Clinical Chemistry and Toxicology, Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Melissa Cavalheiro
authors.initials: MC
authors.lastname: Tourino
authors.forename: Edson Mendes
authors.initials: EM
authors.lastname: de Oliveira
authors.forename: Luziane Potrich
authors.initials: LP
authors.lastname: Bellé
authors.forename: Franciele Hinterholz
authors.initials: FH
authors.lastname: Knebel
authors.forename: Renata Chaves
authors.initials: RC
authors.lastname: Albuquerque
authors.forename: Felipe Augusto
authors.initials: FA
authors.lastname: Dörr
authors.forename: Sabrina Sayori
authors.initials: SS
authors.lastname: Okada
authors.forename: Silene
authors.initials: S
authors.lastname: Migliorini
authors.forename: Irene Silva
authors.initials: IS
authors.lastname: Soares
authors.forename: Ana
authors.initials: A
authors.lastname: Campa
mesh_terms: D001667:Binding, Competitive; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018920:Coculture Techniques; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D057075:Enzyme Assays; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007700:Kinetics; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology; D004130:N,N-Dimethyltryptamine / Q000494:pharmacology*; D011485:Protein Binding; D011994:Recombinant Proteins / Q000378:metabolism; D014363:Tryptamines / Q000494:pharmacology*; D014364:Tryptophan / Q000378:metabolism
chemical_list: D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D011994:Recombinant Proteins; D014363:Tryptamines; C030820:tryptamine; D014364:Tryptophan; D004130:N,N-Dimethyltryptamine
keywords: immune escape; kynurenine pathway; tolerance; tryptophan metabolism; tumor growth