查找使用阿拉丁产品的科研文献

Coibamide A kills cancer cells through inhibiting autophagy

Wenli Shi,Danyi Lu,Chunlei Wu,Meiqing Li,Zhihao Ding,Yanyan Li,Binghua Chen,Xian Lin,Wu Su,Ximing Shao,Zhihui Xia,Lijing Fang,Ke Liu,Hongchang Li

Natural products are useful tools for biological mechanism research and drug discovery. Due to the excellent tumor cell growth inhibitory profile and sub-nanomolar potency, Coibamide A (CA), an N-methyl-stabilized depsipeptide isolated from marine cyanobacterium , has been considered as a promising lead compound for cancer treatment. However, the molecular anti-cancer mechanism of the action of CA remains unclear. Here, we showed that CA treatment induced caspase-independent cell death in breast cancer cells. CA treatment also led to severe lysosome defects, which was ascribed to the impaired glycosylation of lysosome membrane protein LAMP1 and LAMP2 . As a consequence, the autophagosome-lysosome fusion was blocked upon CA treatment. In addition, we presented evidence that this autophagy defect partially contributed to the CA treatment-induced tumor cell death. Together, our work uncovers a novel mechanism underlying the anti-cancer action of CA, which will promote its further application for cancer therapy.