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The efforts for therapeutic targeting of the aryl hydrocarbon receptor (AhR) have emerged in recent years. We investigated the effects of available antimigraine triptan drugs, having an indole core in their structure, on AhR signaling in human hepatic and intestinal cells. Activation of AhR in reporter gene assays was observed for Avitriptan and to a lesser extent for Donitriptan, while other triptans were very weak or no activators of AhR. Using competitive binding assay and by homology docking, we identified Avitriptan as a low-affinity ligand of AhR. Avitriptan triggered nuclear translocation of AhR and increased binding of AhR in CYP1A1 promotor DNA, as revealed by immune-fluorescence microscopy and chromatin immune-precipitation assay, respectively. Strong induction of CYP1A1 mRNA was achieved by Avitriptan in wild type but not in AhR-knockout, immortalized human hepatocytes, implying that induction of CYP1A1 is AhR-dependent. Increased levels of CYP1A1 mRNA by Avitriptan were observed in human colon carcinoma cells LS180 but not in primary cultures of human hepatocytes. Collectively, we show that Avitriptan is a weak ligand and activator of human AhR, which induces the expression of CYP1A1 in a cell-type specific manner. Our data warrant the potential off-label therapeutic application of Avitriptan as an AhR-agonist drug.
Pubmed ID: 32316498
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Collection of information about chemical structures and biological properties of small molecules and siRNA reagents hosted by the National Center for Biotechnology Information (NCBI).
View all literature mentionsPrivately held company that develops and produces antibodies, ELISA kits, ChIP kits, proteomic kits, and other related reagents used to study cell signaling pathways that impact human health.
View all literature mentionsCommercial instrument and chemical vendor. Developer and manufacturer of specialized technological products for life science research and clinical diagnostics markets.
View all literature mentionsAn open-source program for doing molecular docking.
View all literature mentionsA software package created to perform molecular dynamics. It is primarily designed for biochemical molecules like proteins, lipids and nucleic acids that have many complicated bonded interactions, but it can also be used for research on non-biological systems, such as polymers.
View all literature mentionsWeb server as integrated platform for automated protein structure and function prediction. Used for protein 3D structure prediction. Resource for automated protein structure prediction and structure-based function annotation.
View all literature mentionsSoftware tool for automatic generation of multiple 2D ligand-protein interaction diagrams from 3D coordinates. Diagrams portray hydrogen-bond interaction patterns and hydrophobic contacts between ligand(s) and main-chain or side-chain elements of protein. Used for drug discovery for analyzing series of small molecules binding to same protein target, single ligand binding to homologous proteins, or where both protein and ligand change.
View all literature mentionsSoftware graphical user interface to help to set up which bonds will treated as rotatable in the ligand and to analyze dockings. Used for automated docking with selective receptor flexibility. Designed to predict how small molecules, such as substrates or drug candidates, bind to receptor of known 3D structure.
View all literature mentionsCell line LS180 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line Hepa-1c1c7 is a Cancer cell line with a species of origin Mus musculus (Mouse)
View all literature mentionsCell line LS174T is a Cancer cell line with a species of origin Homo sapiens (Human)
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