Tryptamine and dimethyltryptamine inhibit indoleamine 2,3 dioxygenase and increase the tumor-reactive effect of peripheral blood mononuclear cells

Autor(es)

Tourino, Melissa Cavalheiro ^[1] ; de Oliveira, Edson Mendes ^[1] ; Belle, Luziane Potrich ^[1] ; Knebel, Franciele Hinterholz ^[1] ; Albuquerque, Renata Chaves ^[1] ; Doerr, Felipe Augusto ^[1] ; Okada, Sabrina Sayori ^[1] ; Migliorini, Silene ^[1] ; Soares, Irene Silva ^[1] ; Campa, Ana ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Fac Pharmaceut Sci, Dept Clin Chem & Toxicol, BR-05508900 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Cell Biochemistry and Function; v. 31, n. 5, p. 361-364, JUL 2013.
• Citações Web of Science: 17

Resumo

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. (AU)

• Processo FAPESP: 09/14632-3 - Via das quinureninas versus via serotonérgica: participação na comunicação entre células do sistema imune e no imune escape de tumores
• Beneficiário: Ana Campa
• Modalidade de apoio: Auxílio à Pesquisa - Regular