Abstract |
Epothilone B (EpoB) is an FDA-approved anti-neoplastic agent used to treat metastatic breast cancer; However, its usage is limited due to its severe peripheral neurotoxicity. Ferroptosis is a type of programmed cell death triggered by iron accumulation, and it is induced by lipid peroxidation. Ferroptosis has been linked to multiple diseases, including cancer, type 2 diabetes, and neurodegenerative disorders. Here, we assessed the role of ferroptosis in EpoB-induced neural dysfunction. Our results revealed that EpoB induced ferroptosis, which was significantly reduced by the ferroptosis inhibitor Fer-1. In addition, EpoB decreased the mitochondrial membrane potential and the cytochrome c levels in Schwann cells (SCs). The antioxidant MitoTEMPO, which targets the mitochondria, reduced ferroptosis brought on by EpoB. Moreover, we demonstrated that in vivo EpoB-induced myelin degradation and neuronal dysfunction were mitigated by SRT1720, a Sirtuin1 ( SIRT1) activator, and by SRT1720 and mitoquinone mesylate ( mitoQ). Our results suggest that ferroptosis elicited by EpoB is caused by mitochondrial damage mediated by SIRT1 inactivation and that ferroptosis causes neural dysfunction following EpoB.
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Authors | Zhuowen Liang, Na Zhang, Xuankang Wang, Jiawei Zhang, Kun Li, Tao Lei |
Journal | European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences
(Eur J Pharm Sci)
Vol. 181
Pg. 106350
(Feb 01 2023)
ISSN: 1879-0720 [Electronic] Netherlands |
PMID | 36496165
(Publication Type: Journal Article)
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Copyright | Copyright © 2022. Published by Elsevier B.V. |
Chemical References |
- epothilone B
- Reactive Oxygen Species
- Sirtuin 1
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Topics |
- Humans
- Ferroptosis
- Reactive Oxygen Species
(metabolism)
- Sirtuin 1
(metabolism)
- Diabetes Mellitus, Type 2
(metabolism)
- Mitochondria
(metabolism)
- Schwann Cells
(metabolism)
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