Journal
BIOORGANIC & MEDICINAL CHEMISTRY
Volume 34, Issue -, Pages -Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2021.116041
Keywords
Madangamine; Marine natural product; Antiproliferative activity; Autophagy; Lysosomotropic agent
Funding
- Mizutani Foundation for Glycoscience [18K06137]
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The study found that madangamine A has strong anti-proliferative activity against human cancer cell lines by inhibiting lysosome function.
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.
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