坏死性下垂
SIRT3
麦角新碱
细胞生物学
癌症研究
程序性细胞死亡
生物
结直肠癌
癌症
化学
医学
生物化学
内科学
细胞凋亡
抗氧化剂
乙酰化
锡尔图因
基因
作者
Nunzia D’Onofrio,Elisa Martino,Anna Balestrieri,Luigi Mele,Domenico Cautela,Domenico Castaldo,Maria Luisa Balestrieri
出处
期刊:FEBS Letters
[Wiley]
日期:2022-02-05
卷期号:596 (10): 1313-1329
被引量:25
标识
DOI:10.1002/1873-3468.14310
摘要
Ergothioneine (Egt) is a dietary amino acid which acts as an antioxidant to protect against ageing‐related diseases. We investigated the anti‐cancer properties of Egt in colorectal cancer cells (CRC). Egt treatment exerted cytotoxicity in a dose‐dependent manner, induced reactive oxygen species accumulation, loss of mitochondrial membrane potential and upregulation of the histone deacetylase SIRT3. Immunoblotting analysis indicated that the cell death occurred via necroptosis through activation of the RIP1/RIP3/MLKL pathway. An immunoprecipitation assay unveiled that the interaction between the terminal effector in necroptotic signalling MLKL and SIRT3 increased during the Egt treatment. SIRT3 gene silencing blocked the upregulation of MLKL and abolished the ability of Egt to induce necroptosis. The SIRT3–MLKL interaction may mediate the necroptotic effects of Egt in CRC, suggesting the potential of this dietary amino thione in the prevention of CRC.
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