1. Coibamide A kills cancer cells through inhibiting autophagy
- Author
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Danyi Lu, Wenli Shi, Chunlei Wu, Zhihao Ding, Zhihui Xia, Lijing Fang, Xian Lin, Meiqing Li, Binghua Chen, Yanyan Li, Hongchang Li, Ximing Shao, Wu Su, and Ke Liu
- Subjects
0301 basic medicine ,Programmed cell death ,Biophysics ,Antineoplastic Agents ,Breast Neoplasms ,Biochemistry ,03 medical and health sciences ,0302 clinical medicine ,Cell Line, Tumor ,Depsipeptides ,Lysosome ,Autophagy ,medicine ,Humans ,Molecular Biology ,Cell Proliferation ,Depsipeptide ,LAMP2 ,LAMP1 ,Drug discovery ,Chemistry ,Autophagosomes ,Cell Biology ,030104 developmental biology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Cancer cell ,Cancer research ,Female ,Lysosomes ,Signal Transduction - Abstract
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.
- Published
- 2021