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Brusatol inhibits amyloid‐β‐induced neurotoxicity in U‐251 cells via regulating the Nrf2/HO‐1 pathway
Author(s) -
Liu Xin,
Xu HuaWen,
Zhang YueQi,
Wang Peng,
Gao Wei
Publication year - 2019
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.28341
Subject(s) - neurotoxicity , apoptosis , pi3k/akt/mtor pathway , chemistry , reactive oxygen species , mtt assay , cytotoxic t cell , pharmacology , glioma , cytotoxicity , programmed cell death , cell culture , protein kinase b , cell , microbiology and biotechnology , biochemistry , biology , cancer research , in vitro , toxicity , genetics , organic chemistry
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.