| Autor: |
Melissa Cavalheiro, Tourino, Edson Mendes, de Oliveira, Luziane Potrich, Bellé, Franciele Hinterholz, Knebel, Renata Chaves, Albuquerque, Felipe Augusto, Dörr, Sabrina Sayori, Okada, Silene, Migliorini, Irene Silva, Soares, Ana, Campa |
| Rok vydání: |
2013 |
| Předmět: |
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| Zdroj: |
Cell biochemistry and function. 31(5) |
| ISSN: |
1099-0844 |
| Popis: |
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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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