一氧化氮
脂质过氧化
自噬
化学
一氧化氮合酶
细胞生物学
细胞凋亡
瓜氨酸
氧化应激
下调和上调
GPX4
癌细胞
溶酶体
程序性细胞死亡
精氨酸
生物化学
癌症研究
生物
癌症
酶
过氧化氢酶
氨基酸
谷胱甘肽过氧化物酶
基因
有机化学
遗传学
作者
Li Jiang,Hao Zheng,Qinying Lyu,Shotaro Hayashi,Kotaro Sato,Yoshitaka Sekido,Kae Nakamura,Hiromasa Tanaka,Kenji Ishikawa,Hiroaki Kajiyama,Masaaki Mizuno,Masaru Hori,Shinya Toyokuni
出处
期刊:Redox biology
[Elsevier]
日期:2021-07-01
卷期号:43: 101989-101989
被引量:51
标识
DOI:10.1016/j.redox.2021.101989
摘要
Non-thermal plasma (NTP), an engineered technology to generate reactive species, induces ferroptosis and/or apoptosis specifically in various-type cancer cells. NTP-activated Ringer's lactate (PAL) is another modality for cancer therapy at preclinical stage. Here we found that PAL induces selective ferroptosis of malignant mesothelioma (MM) cells, where non-targeted metabolome screening identified upregulated citrulline-nitric oxide (.NO) cycle as a PAL target. .NO probe detected biphasic peaks transiently at PAL exposure with time-dependent increase, which was responsible for inducible . NO synthase (iNOS) overexpression through NF-κB activation. .NO and lipid peroxidation occupied lysosomes as a major compartment with increased TFEB expression. Not only ferrostatin-1 but inhibitors for . NO and/or iNOS could suppress this ferroptosis. PAL-induced ferroptosis accompanied autophagic process in the early phase, as demonstrated by an increase in essential amino acids, LC3B-II, p62 and LAMP1, transforming into the later phase with boosted lipid peroxidation. Therefore, .NO-mediated lysosomal impairment is central in PAL-induced ferroptosis.
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