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Disulfiram/Copper Activates ER Stress to Promote Immunogenic Cell Death of Oral Squamous Cell Carcinoma

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Abstract

Disulfiram/copper complex (DSF/Cu) was found to have anti-tumor effects in a range of malignancies, including oral squamous cell carcinoma (OSCC), yet its precise mechanism remains unknown. It has been shown that ER stress enhances immunogenic cell death (ICD) in tumor cells, as it can influence the anti-cancer immune system favorably. In this study, we reported that DSF/Cu exhibited a marked inhibitory effect on the growth of OSCC cells, accompanied by cell apoptosis. OSCC cells treated with DSF/Cu showed the hallmarks of immunogenic cell death (ICD), including surface expression of calreticulin (CRT), heat shock protein 70 (HSP70), high mobility-group box 1 (HMGB-1) and adenosine triphosphate (ATP), thus, eliciting the maturation and activation of dendritic cells. Furthermore, we showed DSF/Cu-induced endoplasmic reticulum (ER) stress in OSCC cells. In vivo, results demonstrate that DSF/Cu inhibits tumor growth locally and alters the intratumoral immune cell infiltration and response. In conclusion, DSF/Cu suppresses OSCC development by inducing ICD and ER stress. DSF/Cu has the potential to be a new anti-tumor immunotherapy concept because of its ability to elicit ICD.

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Data Availability

The datasets used or analyzed during the current study are available from the corresponding author upon reasonable request.

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Acknowledgements

We would like to acknowledge the reviewers for their helpful comments on this paper.

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Authors and Affiliations

  1. Department of Stomatology, Tianjin First Central Hospital, Tianjin, 300190, China

    Yanjuan Zhao & Bo Zhao

  2. Department of Stomatology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, 300190, China

    Shujin Zhu

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  1. Yanjuan Zhao
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  2. Bo Zhao
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Contributions

Y.Z. and S.Z. designed and performed the research; Y.Z. and B.Z. analyzed the data; Y.Z. wrote the manuscript. All authors read and approved the final manuscript.

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Correspondence to Shujin Zhu.

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The authors declare no competing interests.

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All animal experiments have been reviewed and approved by the Institutional Ethics Review Committee of the Tianjin First Central Hospital.

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Zhao, Y., Zhao, B. & Zhu, S. Disulfiram/Copper Activates ER Stress to Promote Immunogenic Cell Death of Oral Squamous Cell Carcinoma. Cell Biochem Biophys (2024). https://doi.org/10.1007/s12013-024-01283-z

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