1,8-cineol inhibits the Wnt/β-catenin signaling pathway through GSK-3 dephosphorylation in nasal polyps of chronic rhinosinusitis patients.

Autor: Bruchhage KL; Department of Otorhinolaryngology, University Medical Center Schleswig-Holstein, Campus Lübeck, Lübeck, Germany., Koennecke M; Department of Otorhinolaryngology, University Medical Center Schleswig-Holstein, Campus Lübeck, Lübeck, Germany., Drenckhan M; Department of Otorhinolaryngology, University Medical Center Schleswig-Holstein, Campus Lübeck, Lübeck, Germany., Plötze-Martin K; Department of Otorhinolaryngology, University Medical Center Schleswig-Holstein, Campus Lübeck, Lübeck, Germany., Pries R; Department of Otorhinolaryngology, University Medical Center Schleswig-Holstein, Campus Lübeck, Lübeck, Germany., Wollenberg B; Department of Otorhinolaryngology, University Medical Center Schleswig-Holstein, Campus Lübeck, Lübeck, Germany. Electronic address: Barbara.Wollenberg@uksh.de.
Jazyk: angličtina
Zdroj: European journal of pharmacology [Eur J Pharmacol] 2018 Sep 15; Vol. 835, pp. 140-146. Date of Electronic Publication: 2018 Aug 03.
DOI: 10.1016/j.ejphar.2018.07.060
Abstrakt: Chronic rhinosinusitis with nasal polyps (CRSwNP) represents a benign neoplasm of the nasal mucosa, which leads to a decreased breathing capacity and reduced olfaction. The pathogenesis and the molecular mechanisms driving nasal polyps are not very well known. GSK-3 is involved in the regulation of various biosynthetic pathways and various kinases are able to regulate the GSK-3. Therefore, we investigated the effect of the monoterpene oxide 1,8-cineol on the regulation of the Wnt/β-catenin signaling pathway with its central regulator protein GSK-3 in vitro. We determined GSK-3 expression and phosphorylation as well as the expression of negative regulators (Akt and SGK) and downstream activation of β-catenin in nasal polyps of patients with CRSwNP by immunohistochemistry and Western blot experiments. In this study we demonstrated for the first time, that 1,8-cineol acts as a potential inhibitor of the Wnt/β-catenin signaling pathway, by affecting the inhibitory phosphorylation of GSK-3, which is the key regulator of the β-catenin activity. Our data provide novel insights in the regulatory networks responsible for the progression of CRSwNP and furthermore represent a new mechanism of 1,8-cineol activity, which may lead to novel treatment approaches to this natural drug.
(Copyright © 2018 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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