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

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

Bioorganic & medicinal chemistry (2021-02-08)
Kazuki Miura, Sayaka Kawano, Takahiro Suto, Takaaki Sato, Noritaka Chida, Siro Simizu
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
抗LC3B ウサギ宿主抗体, ~1 mg/mL, affinity isolated antibody, buffered aqueous solution
Sigma-Aldrich
Anti-CTSB antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution