論文

国際誌
2021年2月2日

S1PR3-G12-biased agonist ALESIA targets cancer metabolism and promotes glucose starvation.

Cell chemical biology
  • 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

記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/j.chembiol.2021.01.004

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.

リンク情報
DOI
https://doi.org/10.1016/j.chembiol.2021.01.004
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/33561428
ID情報
  • DOI : 10.1016/j.chembiol.2021.01.004
  • PubMed ID : 33561428

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