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J Cell Biochem. 2019 Jan 10. doi: 10.1002/jcb.28341. [Epub ahead of print]

Brusatol inhibits amyloid-β-induced neurotoxicity in U-251 cells via regulating the Nrf2/HO-1 pathway.

Author information

1
Department of Neurology, ZouCheng Branch of Affiliated Hospital of Jining Medical University, Jining, Shandong, China.
2
Department of Neurosurgery, ZouCheng Branch of Affiliated Hospital of Jining Medical University, Jining, Shandong, China.
3
Department of Neurology, WeiFang People's Hospital, WeiFang, Shandong, China.
4
Department of Neurology, LiaoCheng Third People's Hospital, LiaoCheng, Shandong, China.

Abstract

Amyloid-β (Aβ) has been reported to cause oxidative damage of neurons leading to neurotoxicity in a variety of diseases and cancers. As an anticancer drug, brusatol (BR) has been shown to have potent cytotoxic effects on various cancer cell lines. In this study, the effect and mechanism of BR on Aβ-induced neurotoxicity was investigated in U-251 glioma cells. Using the MTT assay, the results suggest that BR ameliorated cell injury induced by Aβ in U-251 cells. After running Hoechst and Western blot assays, BR prevented cell apoptosis induced by Aβ in U-251 cells. In addition, BR inhibited the increased reactive oxygen species and mitochondrial membrane potential levels induced by Aβ in U-251 cells using the DCFH-DA and Rh123 method. Furthermore, BR induced the Nrf2/HO-1 pathway by inhibiting the PI3K/AKT/mTOR pathway to inhibit neurotoxicity elicited by Aβ. These results suggest that brustasol is a valuable potential antitumor drug available for chemotherapy.

KEYWORDS:

Nrf2/HO-1 pathway; U-251 cells; amyloid-β (Aβ); brusatol (BR); neurotoxicity

PMID:
30629288
DOI:
10.1002/jcb.28341

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