Abstract
Background
Ovarian cancer (OV) is a gynecologic tumor with high mortality due to its drug resistance. In most cases, simple standard care is not satisfactory. Ferroptosis as a non-apoptotic form of cell death may contribute to the selective elimination of certain tumor cells. Therefore, ferroptosis has been considered to be potential therapy in anti-tumor.
Objective
Here, we report that erastin inhibits OV cell viability by inducing ferroptosis and identified the ferroptosis resistance effect of Nrf2 in OV.
Results
We demonstrated that erastin-induced cells release more Fe2+, malondialdehyde (MDA), and less glutathione (GSH). Nevertheless, we found that erastin-induced ferroptosis in OV cells was inhibited by overexpressed Nrf2. Mechanistically, Nrf2 promotes system xc-, increases intracellular glutamate and GSH, and thus resists tumor ferroptosis. Specifically, Nrf2 promotes system XC mainly by increasing the expression of SLC7A11.
Conclusion
This study revealed a novel cancer-promoting mechanism of Nrf2, mainly enhanced ferroptosis resistance in OV.
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Acknowledgements
We greatly appreciate the support from the Chongqing fourth people's Hospital and Chongqing General Hospital.
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YL performed experiments and participated in the initial draft. RY performed experiments and participated in the initial draft. ML performed experiments and analyzed the data. CC designed the study and supervised the progress. All authors have read and approved the manuscript.
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Yongkang Li declares he has no conflict of interest. Rong Yin declares she has no conflict of interest. Miao Liang declares she has no conflict of interest. Cheng Chen declares he has no conflict of interest.
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The present study was approved by the Ethics Committee of Chongqing General Hospital. The research has been carried out in accordance with the World Medical Association Declaration of Helsinki.
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Li, Y., Yin, R., Liang, M. et al. Nrf2 suppresses erastin-induced ferroptosis through activating system Xc(-) in ovarian cancer. Mol. Cell. Toxicol. 20, 85–95 (2024). https://doi.org/10.1007/s13273-022-00322-1
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DOI: https://doi.org/10.1007/s13273-022-00322-1