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Methuosis Contributes to Jaspine-B-Induced Cell Death
Núria Bielsa1, Mireia Casasampere1, Jose Luis Abad1
1Research Unit on BioActive Molecules, Department of Biological Chemistry, Institute for Advanced Chemistry of Catalonia (IQAC-CSIC), 08034 Barcelona, Spain.
International Journal of Molecular Sciences
|July 9, 2022
Summary
Jaspine B induces programmed cell death called methuosis in lung cancer cells by causing cytoplasmic vacuolation. This process involves 5' AMP-activated protein kinase (AMPK) activation, independent of the PI3K/Akt/mTORC1 pathway.
Area of Science:
- Cell Biology
- Molecular Biology
- Cancer Research
Background:
- Methuosis is a programmed cell death characterized by cytoplasmic vacuolation.
- Jaspine B (JB), a sphingolipid derivative, induces vacuolation and cytotoxicity in cancer cells.
- Lung adenocarcinoma A549 cells with K-Ras mutations are a relevant model for studying JB's effects.
Purpose of the Study:
- Investigate the mechanism of Jaspine B-induced cytotoxicity in A549 cells.
- Elucidate the signalling pathways involved in JB-induced cytoplasmic vacuolation and methuosis.
- Determine the role of AMPK and PI3K/Akt/mTORC1 pathways in JB's effects.
Main Methods:
- Cell viability assays and microscopy (phase contrast, confocal, transmission electron) to assess JB effects.
- Flow cytometry for apoptosis analysis and LC3-II/GFP-LC3-II analysis for autophagy monitoring.
- Macropinocytosis assessment using Lucifer yellow uptake and gene knockout (ATG5, BAX/BAK) in MEFs.
Main Results:
- Jaspine B induced significant cytoplasmic vacuolation and methuosis in A549 cells, leading to cytotoxicity.
- AMPK activation was observed in JB-treated cells, suggesting its involvement in vacuolation.
- The PI3K/Akt/mTORC1 pathway was not found to be essential for JB-induced vacuolation.
Conclusions:
- Jaspine B triggers methuosis and cytotoxicity in lung adenocarcinoma cells.
- AMPK activation plays a role in Jaspine B-induced cytoplasmic vacuolation.
- JB's mechanism of action offers potential therapeutic strategies for K-Ras-mutant lung cancers.
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