Identification of madangamine A as a novel lysosomotropic agent to inhibit autophagy

Kazuki Miura, Sayaka Kawano, Takahiro Suto, Takaaki Sato, Noritaka Chida, Siro Simizu

研究成果: Article査読

3 被引用数 (Scopus)

抄録

Madangamines are marine natural products isolated from Xestospongia ingens, and madangamine A–E with a different D-ring structure have been reported. We have reported that madangamine A has strong anti-proliferative activity against various human cancer cell lines. In this study, to clarify the anti-proliferative activity of madangamine A, we searched for molecular target of the madangamine A in human cells. Treatment with madangamine A increased the levels of LC3-II and p62, autophagy-related proteins, concomitant with growth inhibition. Moreover, madangamine A resulted in lysosome enlargement and increase in lysosomal pH, which are same phenomena observed in chloroquine-treated cells. These results suggest that madangamine A is a novel lysosome inhibitor, and the anti-proliferative activity of madangamine A is due to the inhibition of lysosome function.

本文言語English
論文番号116041
ジャーナルBioorganic and Medicinal Chemistry
34
DOI
出版ステータスPublished - 2021 3 15

ASJC Scopus subject areas

  • 生化学
  • 分子医療
  • 分子生物学
  • 薬科学
  • 創薬
  • 臨床生化学
  • 有機化学

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