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

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/beta-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 beta-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/beta-catenin signaling pathway, by affecting the inhibitory phosphorylation of GSK-3, which is the key regulator of the beta-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.