Vermonden, Perrine and Martin, Manon and Glowacka, Katarzyna and Neefs, Ineke and Ecker, Josef and Höring, Marcus and Liebisch, Gerhard and Debier, Cathy and Feron, Olivier and Larondelle, Yvan (2024) Phospholipase PLA2G7 is complementary to GPX4 in mitigating punicic-acid-induced ferroptosis in prostate cancer cells. ISCIENCE, 27 (5): 109774. ISSN 2589-0042
Full text not available from this repository. (Request a copy)Abstract
Ferroptosis is a cell death pathway that can be promoted by peroxidizable polyunsaturated fatty acids in cancer cells. Here, we investigated the mechanisms underlying the toxicity of punicic acid (PunA), an isomer of conjugated linolenic acids (CLnAs) bearing three conjugated double bonds highly prone to peroxidation, on prostate cancer (PCa) cells. PunA induced ferroptosis in PCa cells and triggered massive lipidome remodeling, more strongly in PC3 androgen -negative cells than in androgen -positive cells. The greater sensitivity of androgen -negative cells to PunA was associated with lower expression of glutathione peroxidase 4 (GPX4). We then identified the phospholipase PLA2G7 as a PunA-induced ferroptosis suppressor in PCa cells. Overexpressing PLA2G7 decreased lipid peroxidation levels, suggesting that PLA2G7 hydrolyzes hydroperoxide-containing phospholipids, thus preventing ferroptosis. Importantly, overexpressing both PLA2G7 and GPX4 strongly prevented PunA-induced ferroptosis in androgen -negative PCa cells. This study shows that PLA2G7 acts complementary to GPX4 to protect PCa cells from CLnAinduced ferroptosis.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ACTIVATING-FACTOR ACETYLHYDROLASE; POMEGRANATE SEED OIL; DEATH; DIFFERENTIATION; PURIFICATION; ACSL4 |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Klinische Chemie und Laboratoriumsmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Jan 2026 09:16 |
| Last Modified: | 14 Jan 2026 09:16 |
| URI: | https://pred.uni-regensburg.de/id/eprint/64357 |
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