Bioenergetic and proteomic profiling to screen small molecule inhibitors that target cancer metabolisms

Yushi Futamura, Makoto Muroi, Harumi Aono, Makoto Kawatani, Marina Hayashida, Tomomi Sekine, Toshihiko Nogawa, Hiroyuki Osada*

*この研究の対応する著者

研究成果: Article査読

14 被引用数 (Scopus)

抄録

Cancer cells can reprogram their metabolic machinery to survive. This altered metabolism, which is distinct from the metabolism of normal cells, is thought to be a possible target for the development of new cancer therapies. In this study, we constructed a screening system that focuses on bioenergetic profiles (specifically oxygen consumption rate and extracellular acidification rate) and characteristic proteomic changes. Thus, small molecules that target cancer-specific metabolism were investigated. We screened the chemical library of RIKEN Natural Products Depository (NPDepo) and found that unantimycin A, which was recently isolated from the fraction library of microbial metabolites, and NPL40330, which is derived from a chemical library, inhibit mitochondrial respiration. Furthermore, we developed an in vitro reconstitution assay method for mitochondrial electron transport chain using semi-intact cells with specific substrates for each complex of the mitochondrial electron transport chain. Our findings revealed that NPL40330 and unantimycin A target mitochondrial complexes I and III, respectively.

本文言語English
ページ(範囲)28-37
ページ数10
ジャーナルBiochimica et Biophysica Acta - Proteins and Proteomics
1867
1
DOI
出版ステータスPublished - 2019 1月
外部発表はい

ASJC Scopus subject areas

  • 分析化学
  • 生物理学
  • 生化学
  • 分子生物学

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