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

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

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

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.

Original languageEnglish
Article number116041
JournalBioorganic and Medicinal Chemistry
Volume34
DOIs
Publication statusPublished - 2021 Mar 15

Keywords

  • Antiproliferative activity
  • Autophagy
  • Lysosomotropic agent
  • Madangamine
  • Marine natural product

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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