TY - JOUR
T1 - Identification of madangamine A as a novel lysosomotropic agent to inhibit autophagy
AU - Miura, Kazuki
AU - Kawano, Sayaka
AU - Suto, Takahiro
AU - Sato, Takaaki
AU - Chida, Noritaka
AU - Simizu, Siro
N1 - Funding Information:
We thank Mr. Yuya Okuyama for a valuable assistant. This work was supported by a Grant-in-Aid for Scientific Research (C) [Grant Number 18K06137 (to SS)] and the Mizutani Foundation for Glycoscience (to SS).
Publisher Copyright:
© 2021 Elsevier Ltd
PY - 2021/3/15
Y1 - 2021/3/15
N2 - 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.
AB - 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.
KW - Antiproliferative activity
KW - Autophagy
KW - Lysosomotropic agent
KW - Madangamine
KW - Marine natural product
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U2 - 10.1016/j.bmc.2021.116041
DO - 10.1016/j.bmc.2021.116041
M3 - Article
C2 - 33549907
AN - SCOPUS:85100392553
VL - 34
JO - Bioorganic and Medicinal Chemistry
JF - Bioorganic and Medicinal Chemistry
SN - 0968-0896
M1 - 116041
ER -
