Coibamide A kills cancer cells through inhibiting autophagy

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 autophagosomelysosome 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. (c) 2021 Elsevier Inc. All rights reserved.

Automated summary

Coibamide A is a promising lead compound for cancer treatment due to its excellent tumor cell growth inhibitory profile and sub-nanomolar potency. It induces caspase-independent cell death and severe lysosome defects, blocking autophagosomelysosome fusion and leading to tumor cell death. These findings provide novel insights into the anti-cancer mechanism of action of Coibamide A.