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Coibamide A kills cancer cells through inhibiting autophagy
- Source :
- Biochemical and Biophysical Research Communications. 547:52-58
- Publication Year :
- 2021
- Publisher :
- Elsevier BV, 2021.
-
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.
- 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
Subjects
Details
- ISSN :
- 0006291X
- Volume :
- 547
- Database :
- OpenAIRE
- Journal :
- Biochemical and Biophysical Research Communications
- Accession number :
- edsair.doi.dedup.....8fa77040277beb97f03b991cff0d2468