| Autor: |
Zoe I. Day, Alyce J. Mayfosh, Amy A. Baxter, Scott A. Williams, Joanne M. Hildebrand, Thomas F. Rau, Ivan K. H. Poon, Mark D. Hulett |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
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| Zdroj: |
Biomolecules, Vol 14, Iss 5, p 555 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2218-273X |
| DOI: |
10.3390/biom14050555 |
| Popis: |
Here, we describe GS-9, a novel water-soluble fatty acid-based formulation comprising L-lysine and arachidonic acid, that we have shown to induce ferroptosis. GS-9 forms vesicle-like structures in solution and mediates lipid peroxidation, as evidenced by increased C11-BODIPY fluorescence and an accumulation of toxic malondialdehyde, a downstream product of lipid peroxidation. Ferroptosis inhibitors counteracted GS-9-induced cell death, whereas caspase 3 and 7 or MLKL knock-out cell lines are resistant to GS-9-induced cell death, eliminating other cell death processes such as apoptosis and necroptosis as the mechanism of action of GS-9. We also demonstrate that through their role of sequestering fatty acids, lipid droplets play a protective role against GS-9-induced ferroptosis, as inhibition of lipid droplet biogenesis enhanced GS-9 cytotoxicity. In addition, Fatty Acid Transport Protein 2 was implicated in GS-9 uptake. Overall, this study identifies and characterises the mechanism of GS-9 as a ferroptosis inducer. This formulation of arachidonic acid offers a novel tool for investigating and manipulating ferroptosis in various cellular and anti-cancer contexts. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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