Pharmacological blockage of the AHR-CYP1A1 axis: a call for in vivo evidence

Coelho, Nuno R.; Pimpão, António B.; Correia, Maria João; Rodrigues, Ticiana C.; Monteiro, Emília C.; Morelló, Judit; Pereira, Sofia A.

doi:10.1007/s00109-021-02163-2

Cited by 28 publications

(10 citation statements)

References 165 publications

(216 reference statements)

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“…Consequently, the effect on the transcriptional activity of the target genes would be opposite to that achieved by wildtype AHRR, leading to the upregulation of the AHR signalling pathway. The expression of CYP1A1, the prototypical target gene of AHR, 28 was exceedingly high in both AHRR:: NCOA2 and AHRR::NCOA3 fusion cases compared to the control. It proved the upregulation of the AHR pathway, which would play an important role in tumorigenesis.…”

Section: Table 3 Immunohistochemical Resultsmentioning

confidence: 86%

Clinicopathologic and genetic characterization of angiofibroma of soft tissue: a study of 12 cases including two cases with AHRR::NCOA3 gene fusion

et al. 2023

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Aims: Angiofibroma of soft tissue (AFST) is a benign tumour characterised by prominent arborizing blood vessels throughout the lesion. Approximately twothirds of AFST cases were reported to have AHRR:: NCOA2 fusion, and only two cases have been reported to have other gene fusions: GTF2I::NCOA2 or GAB1::ABL1. Although AFST is included in fibroblastic and myofibroblastic tumours in the World Health Organization's 2020 classification, histiocytic markers, especially CD163, have been reported to be positive in almost all examined cases, and it still remains the possibility of a fibrohistiocytic nature of the tumour. Therefore, we aimed to clarify the genetic and pathological spectrum of AFST and identify whether histiocytic marker-positive cells were true neoplastic cells. Methods and results: We evaluated 12 AFST cases, which included 10 cases with AHRR::NCOA2 and two with AHRR::NCOA3 fusions. Pathologically, nuclear palisading, which has not been reported in AFST, was detected in two cases. Furthermore, one tumour resected by additional wide resection revealed severe infiltrative growth. Immunohistochemical analysis indicated varying levels of desmin-positive cells in nine cases, whereas CD163-and CD68positive cells were diffusely distributed in all 12 cases. We also performed double immunofluorescence staining and immunofluorescence in situ hybridisation in four resected cases with >10% desmin-positive tumour cells. The results suggested that the CD163positive cells differed from desmin-positive cells with AHRR::NCOA2 fusion in all four cases. Conclusion: Our findings suggested that AHRR:: NCOA3 could be the second most frequent fusion gene, and histiocytic marker-positive cells are not genuine neoplastic cells in AFST.

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Section: Table 3 Immunohistochemical Resultsmentioning

confidence: 86%

Clinicopathologic and genetic characterization of angiofibroma of soft tissue: a study of 12 cases including two cases with AHRR::NCOA3 gene fusion

et al. 2023

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“…The expression of CYP1A1 is a reliable indicator of activation of this pathway ( Hu et al, 2007 ). Chronic diseases can activate the AHR/CYP1A1 pathway, and its inhibition may be beneficial in metabolic and immunological disorders ( Coelho et al, 2022 ).…”

Section: Resultsmentioning

confidence: 99%

“…Several types of AHR antagonists (e.g. CH-223191) have been extensively studied in a variety of disease models in vitro and in vivo, indicating the potential of AHR antagonists as an effective strategy to prevent viral diseases, lung diseases, cardiometabolic diseases and obesity ( Coelho et al, 2022 ). In this study, we demonstrate that PSB suppresses the activation of AHR/CYP1A1 signaling pathway, suggesting that PSB may be an AHR antagonist or CYP1A1 inhibitor and has the corresponding function.…”

Section: Resultsmentioning

confidence: 99%

“…Additionally, some CYP1A1 substrates, such as FICZ, can also act as AHR ligands. Thus, the inhibition of CYP1A1 metabolism can lead to an increase in AHR-mediated CYP1A1 activation ( Coelho et al, 2022 ). In this study, PGE2 was up-regulated, which has also been reported as an AHR ligand that induces CYP1A1, thus increasing its transcription and activity.…”

Section: Resultsmentioning

confidence: 99%

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Pinostrobin from plants and propolis against human coronavirus HCoV-OC43 by modulating host AHR/CYP1A1 pathway and lipid metabolism

Yao

Chen

et al. 2023

Antiviral Research

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“…CYP1A1 is a metabolism-related enzyme regulated by AhR [30]. Various studies have suggested that CYP1A1 overexpression is involved in the development of the cleft palate [31,32]. Overexpression of CYP1A1 mediated by AhR has been reported to inhibit cell proliferation and cause cell death [33].…”

Section: Discussionmentioning

confidence: 99%

Quercetin Reduces the Development of 2,3,7,8-Tetrachlorodibenzo-p-dioxin-Induced Cleft Palate in Mice by Suppressing CYP1A1 via the Aryl Hydrocarbon Receptor

et al. 2022

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Quercetin is a flavonoid with a wide range of pharmacological activities, including anticancer, antioxidant, and anti-inflammatory effects. Since it is a nutrient that can be consumed with a regular diet, quercetin has recently garnered interest. Quercetin acts as a phytochemical ligand for the aryl hydrocarbon receptor (AhR). Cleft lip and palate are among the most frequently diagnosed congenital diseases, and exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) during pregnancy induces cleft palate via AhR. In this study, we investigated the preventive effect of quercetin intake on the TCDD-induced cleft palate and its mechanism of action. The in vivo results suggest that quercetin intake by pregnant mice can prevent cleft palate in fetal mice. In vitro, the addition of TCDD induced a reduction in cell migration and the proliferation of mouse embryonic palatal mesenchymal cells, which was mitigated by the addition of quercetin. The addition of quercetin did not alter the mRNA expression levels of the AhR repressor but significantly suppressed mRNA expression of CYP1A1. In addition, the binding of AhR to a xenobiotic responsive element was inhibited by quercetin, based on a chemically activated luciferase expression assay. In conclusion, our results suggest that quercetin reduces the development of TCDD-induced cleft palate by inhibiting CYP1A1 through AhR.

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Pharmacological blockage of the AHR-CYP1A1 axis: a call for in vivo evidence

Cited by 28 publications

References 165 publications

Clinicopathologic and genetic characterization of angiofibroma of soft tissue: a study of 12 cases including two cases with AHRR::NCOA3 gene fusion

Clinicopathologic and genetic characterization of angiofibroma of soft tissue: a study of 12 cases including two cases with AHRR::NCOA3 gene fusion

Pinostrobin from plants and propolis against human coronavirus HCoV-OC43 by modulating host AHR/CYP1A1 pathway and lipid metabolism

Quercetin Reduces the Development of 2,3,7,8-Tetrachlorodibenzo-p-dioxin-Induced Cleft Palate in Mice by Suppressing CYP1A1 via the Aryl Hydrocarbon Receptor

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