NDLI: 1-Methyl-D-tryptophan activates aryl hydrocarbon receptor, a pathway associated with bladder cancer progression

Content Provider	Springer Nature : BioMed Central
Author	Matheus, Luiz Henrique Gomes Dalmazzo, Stephanie Vanin Brito, Rodrigo Barbosa Oliveira Pereira, Lucas Alves de Almeida, Robson José Camacho, Cleber Pinto Dellê, Humberto
Abstract	Background Indoleamine 2, 3-dioxygenase-1 (IDO1) is a promising target for immunotherapy in bladder cancer (BC). IDO1 breaks-down tryptophan to generate kynurenine derivatives, which may activate the aryl hydrocarbon receptor (AHR). AHR is an important target for carcinogens, but its association with BC progression was unknown. Two IDO1 inhibitors used in clinical trials are 1-methyl-D-tryptophan (MT) and INCB240360. Because MT is an aromatic hydrocarbon, it may be a ligand for AHR. We hypothesized that AHR could be associated with BC progression and that MT could activate AHR in BC. Methods BC patients (n = 165) were selected from the Gene Expression Omnibus database. A cut-off point for relative expression of AHR and cytochrome 450 enzymes (CYP1A1, CYP1A2, and CYP1B1; markers of AHR activation) was determined to compare with the grade, stage, and tumor progression. For in vitro experiments, RT4 (grade 1) and T24 (grade 3) BC cells were incubated with MT and INCB240360 to evaluate the expression of AHR and CYP1A1. Results AHR activation was associated with grade, stage, and progression of BC. T24 cells express more CYP1A1 than RT4 cells. Although IDO1 expression and kynurenine production are elevated in T24 cells concomitantly to CYP1A1 expression, IDO1 inhibitors were not able to decrease CYP1A1 expression, in contrast, MT significantly increased it in both cell lines. Conclusion In conclusion, it is rational to inhibit IDO1 in BC, among other factors because it contributes to AHR activation. However, MT needs to be carefully evaluated for BC because it is an AHR pathway agonist independently of its effects on IDO1.
Related Links	https://bmccancer.biomedcentral.com/counter/pdf/10.1186/s12885-020-07371-6.pdf
Ending Page	7
Page Count	7
Starting Page	1
File Format	HTM / HTML
ISSN	14712407
DOI	10.1186/s12885-020-07371-6
Journal	BMC Cancer
Issue Number	1
Volume Number	20
Language	English
Publisher	BioMed Central
Publisher Date	2020-09-09
Access Restriction	Open
Subject Keyword	Cancer Research Oncology Surgical Oncology Health Promotion and Disease Prevention Biomedicine Medicine Public Health Aryl hydrocarbon receptor Indoleamine 2 3-dioxygenase Bladder cancer Cytochrome P450 enzymes Medicine/Public Health
Content Type	Text
Resource Type	Article
Subject	Cancer Research Oncology Genetics
Journal Impact Factor	3.4/2023
5-Year Journal Impact Factor	3.8/2023

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