Abstract
Accumulating evidence indicates that the disulfiram/copper complex (DSF/Cu) has been shown to have potent antitumor activity against various cancers. This research evaluated the effects and probable mechanisms of DSF/Cu on oral squamous cell carcinoma (OSCC). In this study, we report the toxicity of the DSF/Cu to OSCC both in vitro and in vivo. Our study showed that DSF/Cu reduced the proliferation and clonogenicity of OSCC cells. DSF/Cu also induced ferroptosis. Importantly, we confirmed that DSF/Cu could increase the free iron pool, enhance lipid peroxidation, and eventually result in ferroptosis cell death. Inhibition of NRF2 or HO-1 enhances the sensitivity of OSCC cells to DSF/Cu-induced ferroptosis. DSF/Cu inhibited the xenograft growth of OSCC cells by suppressing the expression of Nrf2/HO-1. In conclusion, these results provide experimental evidence that Nrf2/HO-1 alleviates DSF/Cu-induced ferroptosis in OSCC. We propose that this therapy could be a novel strategy for treating OSCC.
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YZ and SZ designed and performed the research; YZ and SZ analyzed the data; YZ wrote the manuscript. All authors read and approved the final manuscript.
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Zhao, Y., Zhu, S. Nrf2/HO-1 Alleviates Disulfiram/Copper-Induced Ferroptosis in Oral Squamous Cell Carcinoma. Biochem Genet 62, 144–155 (2024). https://doi.org/10.1007/s10528-023-10405-w
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DOI: https://doi.org/10.1007/s10528-023-10405-w