The tubulin inhibitor MG-2477 induces autophagy-regulated cell death, ROS accumulation and activation of FOXO3 in neuroblastoma

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Abstract

Gastrodin (GAS), a phenolic glucoside derived from Gastrodiaelata Blume, has been reported to have anti-inflammatory effect. The aim of this study was to investigate the effects of GAS on LPS-induced acute lung injury in mice. ALI was induced by the intranasal administration of LPS and GAS was given 1 h or 12 h after LPS treatment. The results indicated that GAS treatment markedly attenuated the damage of lung injury induced by LPS. GAS attenuated the activity of myeloperoxidase (MPO) and downregulated the levels of pro-inflammatory cytokines TNF-a, IL-6 and IL-1β in BALF. LPSinduced lung edema and lung function were also reversed by GAS. Furthermore, GAS was found to inhibit LPS-induced inflammatory cells infiltration. In addition, treatment of GAS inhibited LPS-induced NF-κB activation and up-regulated the expression of Nrf2 and HO-1. In conclusion, our results indicated that GAS had anti-inflammatory effects on LPS-induced acute lung injury. The anti-inflammatory mechanism of GAS was through the inhibition of NF-?B and activation of Nrf2 signaling pathways.

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Hagenbuchner, J., Lungkofler, L., Kiechl-Kohlendorfer, U., Viola, G., Ferlin, M. G., Ausserlechner, M. J., & Obexer, P. (2017). The tubulin inhibitor MG-2477 induces autophagy-regulated cell death, ROS accumulation and activation of FOXO3 in neuroblastoma. Oncotarget, 8(19), 32009–32026. https://doi.org/10.18632/oncotarget.16434

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