细胞生物学
PI3K/AKT/mTOR通路
糖酵解
新陈代谢
自噬
碳水化合物代谢
癌症研究
代谢途径
蛋白激酶B
厌氧糖酵解
癌症
瓦博格效应
作者
Masayasu Toyomoto,Asuka Inoue,Kei Iida,Masatsugu Denawa,Isao Kii,Francois Marie Ngako Kadji,Takayuki Kishi,Dohyun Im,Tatsuro Shimamura,Hiroshi Onogi,Suguru Yoshida,So Iwata,Junken Aoki,Takamitsu Hosoya,Masatoshi Hagiwara
出处
期刊:Chemistry & Biology
[Elsevier]
日期:2021-08-19
卷期号:28 (8)
标识
DOI:10.1016/j.chembiol.2021.01.004
摘要
Metabolic activities are altered in cancer cells compared with those in normal cells, and the cancer-specific pathway becomes a potential therapeutic target. Higher cellular glucose consumption, which leads to lower glucose levels, is a hallmark of cancer cells. In an objective screening for chemicals that induce cell death under low-glucose conditions, we discovered a compound, denoted as ALESIA (Anticancer Ligand Enhancing Starvation-induced Apoptosis). By our shedding assay of transforming growth factor α in HEK293A cells, ALESIA was determined to act as a sphingosine-1-phosphate receptor 3-G12-biased agonist that promotes nitric oxide production and oxidative stress. The oxidative stress triggered by ALESIA resulted in the exhaustion of glucose, cellular NADPH deficiency, and then cancer cell death. Intraperitoneal administration of ALESIA improved the survival of mice with peritoneally disseminated rhabdomyosarcoma, indicating its potential as a new type of anticancer drug for glucose starvation therapy.
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