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.

Madangamines 是从Xestospongia ingens 中分离出来的海洋天然产物, 和具有不同 D 环结构的 madangamine A-E 已被报道。我们已经报道了 madangamine A 对各种人类癌细胞系具有很强的抗增殖活性。在本研究中，为了阐明madangamine A的抗增殖活性，我们在人体细胞中寻找madangamine A的分子靶点。用 madangamine A 处理增加了自噬相关蛋白 LC3-II 和 p62 的水平，同时抑制了生长。此外，madangamine A 导致溶酶体增大和溶酶体 pH 值增加，这与在氯喹处理的细胞中观察到的现象相同。这些结果表明，madangamine A 是一种新型的溶酶体抑制剂，madangamine A 的抗增殖活性是由于对溶酶体功能的抑制。