Rutaecarpine Inhibits U87 Glioblastoma Cell Migration by Activating the Aryl Hydrocarbon Receptor Signaling Pathway

Liu, Yiyun; Chen, Yangsheng; Zhu, Ruihong; Xu, Li; Xie, Heidi Qunhui; Zhao, Bin

doi:10.3389/fnmol.2021.765712

Cited by 8 publications

(3 citation statements)

References 92 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[ 53 ] Rutaecarpine can bind aryl hydrocarbon receptor (AhR) and affect the migration of glioblastoma U87 cells. [ 54 ] The binding of routaecarpine with EGFR and JUN may directly inhibit the activity of GBM cells and inhibit EMT.…”

Section: Discussionmentioning

confidence: 99%

Network pharmacology-based screening of the active ingredients and mechanisms of evodiae fructus anti-glioblastoma multiforme

Hao²,

Liu³

et al. 2022

Medicine

View full text Add to dashboard Cite

Background: Evodiae fructus has been shown to have anti-glioblastoma multiforme (GBM) effects. However, its anti-GBM active components and mechanism remain unclear. In this study, the active components of evodiae fructus were screened by network pharmacology to explore the possible molecular mechanism of resistance to GBM. Materials and methods: The main active ingredients of evodiae fructus were derived from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and Batch-traditional Chinese medicine (TCM). TCMSP and Swiss absorption, distribution, metabolism and elimination (ADME) predict genetic targets for ingredients that meet pharmacological criteria. GBM-related targets were obtained from DisGeNet, GeneCards, Online Mendelian Inheritance in Man (OMIM), Therapeutic Target Database (TTD), and TCGA. A Venn diagram was used to obtain the common targets of evodiae fructus and GBM. Protein–protein interaction (PPI) networks and component-disease target networks were constructed using Cytoscape 3.8.1 software for visualization. GBM gene differential expression was visualized by VolcaNoseR, and potential targets were enriched by Gene Ontology (GO) function and annotated by the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway by SRplot. Molecular docking verification was conducted using AutoDock Vina software. Results: According to the screening conditions, 24 active components and 80 drug targets were obtained. The PPI network contains 80 proteins. The molecular docking verification showed the molecular docking affinity of the core active compounds in evodiae fructus with CASP3, JUN, EGFR, and AKT1. Conclusions: This study preliminarily identified the various molecular targets and multiple pathways of evodiae fructus against GBM.

show abstract

Section: Discussionmentioning

confidence: 99%

Network pharmacology-based screening of the active ingredients and mechanisms of evodiae fructus anti-glioblastoma multiforme

Hao²,

Liu³

et al. 2022

Medicine

View full text Add to dashboard Cite

show abstract

“…), is a promising naturally derived AhR agonist. 75 RUT treatment improved IMQ-induced psoriasis-like dermatitis pathology and downregulated the expression of IFN-α, IL-17 A, and IL-23p19 in the skin lesions, as well as their levels in the serum in mice. 76…”

Section: Ahr Agonists: Potential Candidates For Developing New Drugs ...mentioning

confidence: 91%

The Role of Aryl Hydrocarbon Receptor in the Pathogenesis and Treatment of Psoriasis

Lin,

Meng,

Lin

2024

J Cutan Med Surg

View full text Add to dashboard Cite

The pathogenesis of psoriasis is complex. Aryl hydrocarbon receptor (AhR) is a transcription factor that can be bound and activated by structurally diverse ligands and plays an important role in a range of biological processes and in the pathogenesis of different diseases. Recently, the role of AhR in psoriasis has attracted attention. AhR has toxicological functions and physiological functions. The overexpression and activation of AhR induced by the environmental pollutant and exogenous AhR agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) can drive the development of psoriasis. This TCDD-mediated toxicological response disrupts the physiological functions of AhR resulting in skin barrier disorders and the release of inflammatory cytokines, 2 of the pivotal factors of psoriasis. In addition, highly upregulated kynureninase in psoriasis decreases endogenous AhR agonists, thereby weakening the physiological functions of AhR. Activating AhR physiological signalling should be useful in the treatment of psoriasis. Studies have demonstrated that physiological activation of AhR can dampen the severity of psoriasis. The oldest and effective treatment for psoriasis coal tar works by activating AhR, and both new anti-psoriasis drugs tapinarof and benvitimod are formulations of AhR agonist, supporting that activation of AhR can be used as a new strategy for the treatment of psoriasis. Preclinical and preliminary clinical studies have revealed the anti-psoriasis effects of a number of AhR agonists, providing potential candidates for the development of new drugs for the treatment of psoriasis.

show abstract

“…AhR is a cytosolic protein that, upon ligand binding, translocates to the nucleus and, upon heterodimerization with the AhR nuclear translocator (ARNT), binds to the DNA sequence known as the dioxin- or xenobiotic-responsive element. This triggers the transcription of several genes, many of them involved in the metabolism of xenobiotics, such as cytochrome P450 (CYP) 1A1/1A2/1B1, or involved in cell cycle regulation, cell proliferation, inflammation, and apoptosis [ 8 , 9 , 10 , 11 , 12 , 13 ]. One of the most potent activators of AhR is 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, dioxin).…”

Section: Introductionmentioning

confidence: 99%

Aryl Hydrocarbon Receptor (AhR)-Mediated Signaling in iPSC-Derived Human Motor Neurons

et al. 2022

View full text Add to dashboard Cite

Exposure to environmental pollutants and endogenous metabolites that induce aryl hydrocarbon receptor (AhR) expression has been suggested to affect cognitive development and, particularly in boys, also motor function. As current knowledge is based on epidemiological and animal studies, in vitro models are needed to better understand the effects of these compounds in the human nervous system at the molecular level. Here, we investigated expression of AhR pathway components and how they are regulated by AhR ligands in human motor neurons. Motor neurons generated from human induced pluripotent stem cells (hiPSCs) were characterized at the molecular level and by electrophysiology. mRNA levels of AhR target genes, CYP1A1 and CYP1B1 (cytochromes P450 1A1/1B1), and AhR signaling components were monitored in hiPSCs and in differentiated neurons following treatment with AhR ligands, 2,3,7,8,-tetrachlodibenzo-p-dioxin (TCDD), L-kynurenine (L-Kyn), and kynurenic acid (KA), by RT-qPCR. Changes in AhR cellular localization and CYP1A1 activity in neurons treated with AhR ligands were also assessed. The neurons we generated express motor neuron-specific markers and are functional. Transcript levels of CYP1B1, AhR nuclear translocators (ARNT1 and ARNT2) and the AhR repressor (AhRR) change with neuronal differentiation, being significantly higher in neurons than hiPSCs. In contrast, CYP1A1 and AhR transcript levels are slightly lower in neurons than in hiPSCs. The response to TCDD treatment differs in hiPSCs and neurons, with only the latter showing significant CYP1A1 up-regulation. In contrast, TCDD slightly up-regulates CYP1B1 mRNA in hiPSCs, but downregulates it in neurons. Comparison of the effects of different AhR ligands on AhR and some of its target genes in neurons shows that L-Kyn and KA, but not TCDD, regulate AhR expression and differently affect CYP1A1 and CYP1B1 expression. Finally, although TCDD does not significantly affect AhR transcript levels, it induces AhR protein translocation to the nucleus and increases CYP1A1 activity. This is in contrast to L-Kyn and KA, which either do not affect or reduce, respectively, CYP1A1 activity. Expression of components of the AhR signaling pathway are regulated with neuronal differentiation and are differently affected by TCDD, suggesting that pluripotent stem cells might be less sensitive to this toxin than neurons. Crucially, AhR signaling is affected differently by TCDD and other AhR ligands in human motor neurons, suggesting that they can provide a valuable tool for assessing the impact of environmental pollutants.

show abstract

Rutaecarpine Inhibits U87 Glioblastoma Cell Migration by Activating the Aryl Hydrocarbon Receptor Signaling Pathway

Cited by 8 publications

References 92 publications

Network pharmacology-based screening of the active ingredients and mechanisms of evodiae fructus anti-glioblastoma multiforme

Network pharmacology-based screening of the active ingredients and mechanisms of evodiae fructus anti-glioblastoma multiforme

The Role of Aryl Hydrocarbon Receptor in the Pathogenesis and Treatment of Psoriasis

Aryl Hydrocarbon Receptor (AhR)-Mediated Signaling in iPSC-Derived Human Motor Neurons

Contact Info

Product

Resources

About