下调和上调
三氧化二砷
GPX4
细胞凋亡
程序性细胞死亡
化学
细胞毒性
细胞生物学
免疫印迹
癌症研究
谷胱甘肽
生物
氧化应激
生物化学
超氧化物歧化酶
谷胱甘肽过氧化物酶
酶
体外
基因
作者
Chuchu Feng,Yuechao Wu,Yantao Chen,Xi Xiong,Peng Li,Xiaomin Peng,Chunmou Li,Wen-Jun Weng,Yong Zhu,Dun-Hua Zhou,Yang Li
标识
DOI:10.1007/s11033-022-07497-9
摘要
Neuroblastoma (NB) is the most common extracranial tumor in central nervous system threatening children's health with limited therapeutic options. Arsenic trioxide (ATO) has been identified the cytotoxicity in NB cells but the potential mechanism remains unclear. In this study, we attempted to obtain some insight into the mechanisms of cell death induced by ATO in NB cells.Proteomic analyses found that ATO can affect the signaling pathway associated with ferroptosis, including the upregulation of iron absorption (FTL, FTH1, HO-1), ferritinophagy (LC3, P62, ATG7, NCOA4) and modifier of glutathione synthesis (GCLM); downregulation of glutamine synthetase (GS) and GPX4, which was the critical inhibitor of ferroptosis. Western blot analysis revealing GPX4 expression in SK-N-BE (2) cells decreased after treatment with ATO (7.3 µM), resulting in a loss of GPX4 activity. Furthermore, Ferroptosis inhibitor ferrostatin-1 partially blocked ATO-induced cell death.Our study revealed that ATO may induce ferroptosis in neuroblastoma cell SK-N-BE (2) by facilitating the downregulation of GPX4, ultimately resulting in iron-dependent oxidative death.
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