دورية أكاديمية
Metabolic Rewiring toward Oxidative Phosphorylation Disrupts Intrinsic Resistance to Ferroptosis of the Colon Adenocarcinoma Cells
| العنوان: | Metabolic Rewiring toward Oxidative Phosphorylation Disrupts Intrinsic Resistance to Ferroptosis of the Colon Adenocarcinoma Cells |
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| المؤلفون: | Célia Gotorbe, Jérôme Durivault, Willian Meira, Shamir Cassim, Maša Ždralević, Jacques Pouysségur, Milica Vučetić |
| المصدر: | Antioxidants, Vol 11, Iss 12, p 2412 (2022) |
| بيانات النشر: | MDPI AG, 2022. |
| سنة النشر: | 2022 |
| المجموعة: | LCC:Therapeutics. Pharmacology |
| مصطلحات موضوعية: | ferroptosis, glutathione peroxidase 4, ferroptosis suppressor protein 1, colorectal adenocarcinoma, Warburg effect, OXPHOS, Therapeutics. Pharmacology, RM1-950 |
| الوصف: | Glutathione peroxidase 4 (GPX4) has been reported as one of the major targets for ferroptosis induction, due to its pivotal role in lipid hydroperoxide removal. However, recent studies pointed toward alternative antioxidant systems in this context, such as the Coenzyme Q-FSP1 pathway. To investigate how effective these alternative pathways are in different cellular contexts, we used human colon adenocarcinoma (CRC) cells, highly resistant to GPX4 inhibition. Data obtained in the study showed that simultaneous pharmacological inhibition of GPX4 and FSP1 strongly compromised the survival of the CRC cells, which was prevented by the ferroptosis inhibitor, ferrostatin-1. Nonetheless, this could not be phenocopied by genetic deletion of FSP1, suggesting the development of resistance to ferroptosis in FSP1-KO CRC cells. Considering that CRC cells are highly glycolytic, we used CRC Warburg-incompetent cells, to investigate the role metabolism plays in this phenomenon. Indeed, the sensitivity to inhibition of both anti-ferroptotic axes (GPx4 and FSP1) was fully revealed in these cells, showing typical features of ferroptosis. Collectively, data indicate that two independent anti-ferroptotic pathways (GPX4-GSH and CoQ10-FSP1) operate within the overall physiological context of cancer cells and in some instances, their inhibition should be coupled with other metabolic modulators, such as inhibitors of glycolysis/Warburg effect. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 11122412 2076-3921 |
| Relation: | https://www.mdpi.com/2076-3921/11/12/2412; https://doaj.org/toc/2076-3921 |
| DOI: | 10.3390/antiox11122412 |
| URL الوصول: | https://doaj.org/article/6fa95228102c43c2a2c2ebc446150d07 |
| رقم الأكسشن: | edsdoj.6fa95228102c43c2a2c2ebc446150d07 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 11122412 20763921 |
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| DOI: | 10.3390/antiox11122412 |