Identification of madangamine A as a novel lysosomotropic agent to inhibit autophagy.
Antiproliferative activity
Autophagy
Lysosomotropic agent
Madangamine
Marine natural product
Journal
Bioorganic & medicinal chemistry
ISSN: 1464-3391
Titre abrégé: Bioorg Med Chem
Pays: England
ID NLM: 9413298
Informations de publication
Date de publication:
15 03 2021
15 03 2021
Historique:
received:
05
12
2020
revised:
18
01
2021
accepted:
20
01
2021
pubmed:
8
2
2021
medline:
21
9
2021
entrez:
7
2
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 33549907
pii: S0968-0896(21)00049-3
doi: 10.1016/j.bmc.2021.116041
pii:
doi:
Substances chimiques
Biological Products
0
Heterocyclic Compounds, 4 or More Rings
0
MAP1LC3B protein, human
0
Microtubule-Associated Proteins
0
madangamine A
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
116041Informations de copyright
Copyright © 2021 Elsevier Ltd. All rights reserved.