Miura Kazuki, Kawano Sayaka, Suto Takahiro, Sato Takaaki, Chida Noritaka, Simizu Siro
Department of Applied Chemistry, Faculty of Science and Technology, Keio University, 223-8522, Japan.
Department of Applied Chemistry, Faculty of Science and Technology, Keio University, 223-8522, Japan.
Bioorg Med Chem. 2021 Mar 15;34:116041. doi: 10.1016/j.bmc.2021.116041. Epub 2021 Jan 27.
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.
马丹胺是从巨大海绵（Xestospongia ingens）中分离出的海洋天然产物，并且已经报道了具有不同D环结构的马丹胺A - E。我们已经报道马丹胺A对多种人类癌细胞系具有很强的抗增殖活性。在本研究中，为了阐明马丹胺A的抗增殖活性，我们在人类细胞中寻找马丹胺A的分子靶点。用马丹胺A处理会增加自噬相关蛋白LC3 - II和p62的水平，同时伴随生长抑制。此外，马丹胺A导致溶酶体增大和溶酶体pH值升高，这与用氯喹处理的细胞中观察到的现象相同。这些结果表明马丹胺A是一种新型溶酶体抑制剂，并且马丹胺A的抗增殖活性归因于对溶酶体功能的抑制。
