Identification of madangamine A as a novel lysosomotropic agent to inhibit autophagy. (15th March 2021)

• Record Type: Journal Article
• Authors: Miura, Kazuki; Kawano, Sayaka; Suto, Takahiro; Sato, Takaaki; Chida, Noritaka; Simizu, Siro
• Is Part Of: Bioorganic & medicinal chemistry. Volume 34(2021)
• Publication Date: 2021-03-15
• Subjects: Madangamine -- Marine natural product -- Antiproliferative activity -- Autophagy -- Lysosomotropic agent; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2021.116041
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Highlights: Madangamine A acts as a lysosomotropic agent in cells. Madangamine A is a novel autophagy inhibitor. Inhibition of lysosome function is responsible for anti-proliferative activity of madangamine A. 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.