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Promotion of ferroptosis in head and neck cancer with divalent metal transporter 1 inhibition or salinomycin

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Abstract

Divalent metal transporter 1 (DMT1) inhibitors can selectively kill iron-addicted cancer stem cells by causing lysosomal iron overload, but their role in head and neck cancer (HNC) is unknown. We examined the role of DMT1 inhibition or salinomycin in promoting ferroptosis by lysosomal iron targeting in HNC cells. RNA interference was performed by transfection of siRNA targeting DMT1 or scrambled control siRNA in HNC cell lines. Cell death and viability, lipid peroxidation, iron contents, and molecular expression were compared between the DMT1 silencing or salinomycin group and the control. DMT1 silencing markedly accelerated cell death induced by the ferroptosis inducers. DMT1 silencing marked increases in the labile iron pool, intracellular ferrous and total iron contents, and lipid peroxidation. DMT1 silencing revealed molecular changes in iron starvation response, resulting in increases in TFRC, and decreases in FTH1. Salinomycin treatment also showed similar results to the above DMT1 silencing. DMT1 silencing or salinomycin can promote ferroptosis in HNC cells, suggesting a novel strategy for killing iron-avid cancer cells.

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Funding

This study was supported by the National Research Foundation of Korea (NRF) grant, funded by the Ministry of Science and ICT (MSIT), Republic of Korea (No. 2019R1A2C2002259).

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Authors and Affiliations

  1. Department of Otorhinolaryngology-Head and Neck Surgery, CHA Bundang Medical Center, CHA University, Seongnam, Gyeonggi-do, 13496, Republic of Korea

    Jaewang Lee & Jong-Lyel Roh

  2. Department of Biomedical Science, General Graduate School, CHA University, Seongnam, Republic of Korea

    Jaewang Lee & Jong-Lyel Roh

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  1. Jaewang Lee
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Contributions

JL: conceptualization, methodology, validation, formal analysis, investigation, resources, data curation, and writing (original draft, review and editing). JLR: conceptualization, methodology, validation, formal analysis, investigation, resources, data curation, writing (original draft, review and editing), supervision, and funding acquisition. All authors approved to submit this version for publication.

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Correspondence to Jong-Lyel Roh.

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Lee, J., Roh, JL. Promotion of ferroptosis in head and neck cancer with divalent metal transporter 1 inhibition or salinomycin. Human Cell 36, 1090–1098 (2023). https://doi.org/10.1007/s13577-023-00890-x

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