Analysis of the aril hydrocarbon receptor activation of 1-methyl-tryptophan to ephitelial - mesenchymal transition in human urinary bladder carcinoma cells

• Grant number: 20/10555-3
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: November 01, 2020
• End date: July 31, 2021
• Field of knowledge: Health Sciences - Medicine - Surgery
• Principal Investigator: Humberto Dellê
• Grantee: Caroline Dias de Souza Barbosa
• Host Institution: Universidade Nove de Julho (UNINOVE). Campus Vergueiro. São Paulo , SP, Brazil

Abstract

Bladder cancer is a common neoplasm, being the second most aggressive of the urinary tract. Its aggressiveness depends on its invasive capacity, which is linked to the process of mesenchymal epithelial transition (EMT). Indoleamine 2,3-dioxigenase-1 (IDO1) is an enzyme known for its immunomodulatory action and has been associated with TGF-²1-mediated EMT in bladder carcinoma. From the above, its inhibition as a therapeutic form makes sense and one of the classic forms is through its inhibitor 1-methyl-tryptophan (1-MT). However, our group has shown that 1-MT enhances EMT. Because 1-MT binds to the aryl hydrocarbon receptor (AHR), which is also triggered by IDO1 catabolites and is involved in EMT in tumors in other organs, we raised the hypothesis that 1-MT triggers AHR in bladder carcinoma and, therefore, can contribute to EMT and consequently to tumor progression. Therefore, the present study aims to demonstrate in T24 cells of human bladder carcinoma the use of 1-MT and its association with AHR activation and the EMT process. For this, T24 cells will be incubated with TGF-²1, 1-MT and / or 7-Ketocholesterol (7-KT), an endogenous AHR inhibitor. AHR activation will be analyzed by CYP1A1 expression and EMT will be analyzed by gene expression using real-time PCR and through in vitro invasion analysis. The results may clarify an important mechanism of tumor progression and, if 1-MT has an effect in inducing EMT via AHR, it will be contraindicated for the treatment of bladder cancer.