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Dioscin suppresses tumorigenesis and overcomes radioresistance by promoting ubiquitination-mediated degradation of Mcl-1

Cancer Gene Therapy (2026)Cite this article

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Abstract

Oral squamous cell carcinoma (OSCC) is a prevalent and aggressive malignancy of the oral cavity, with increasing incidence and poor prognosis. Myeloid leukemia 1 (Mcl-1), an anti-apoptotic protein in the BCL-2 family, is critical for tumor development and progression. In this study, we investigated Dioscin, a natural compound, as a potential therapeutic agent for OSCC. Our results demonstrated that Dioscin significantly inhibits cell viability and colony formation in OSCC cell lines. Mechanistically, Dioscin induced intrinsic apoptosis by promoting the ubiquitination and degradation of Mcl-1. Further analysis revealed that Dioscin enhances the interaction between the E3 ligase β-TRCP and Mcl-1 by inhibiting the Akt/GSK3β signaling pathway, resulting in increased phosphorylation of Mcl-1 at Ser159, which drives its destabilization. In vivo, Dioscin notably suppressed OSCC tumor growth, including in sensitive and radioresistant cells, by reducing Mcl-1 levels. These findings highlight the therapeutic potential of Dioscin for OSCC treatment, offering new insights for overcoming radioresistance and improving clinical outcomes in OSCC patients.

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Fig. 1: Mcl-1 plays a crucial role in the tumorigenicity of OSCC cells.
Fig. 2: Dioscin inhibits OSCC cells in vitro.
Fig. 3: Dioscin induces apoptosis of OSCC cells.
Fig. 4: Dioscin induces Mcl-1 degradation and ubiquitination.
Fig. 5: β-TRCP is required for Dioscin-induced ubiquitination of Mcl-1.
Fig. 6: Dioscin restrains cell proliferation via regulating the Akt/GSK3β signaling pathway.
Fig. 7: Dioscin inhibits OSCC cell growth in vivo.
Fig. 8: Dioscin overcomes radioresistance in OSCC cells.

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Data availability

The datasets used and analyzed in this study are available from the corresponding author (W. L.) upon request.

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Funding

This work was supported by the Wisdom Accumulation and Talent Cultivation Project of the Third Xiangya Hospital of Central South University (BJ202203) and the Medical and Health Industry Joint Fund Project of Hunan Provincial Natural Science Foundation (2024JJ9261).

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  1. These authors contributed equally: Qi Liang, Xuecheng Wu.

Authors and Affiliations

  1. Department of Radiology, The Third Xiangya Hospital of Central South University, Changsha, China

    Qi Liang, Xuecheng Wu, Ruirui Wang, Xiaoying Li, Pengfei Guo & Wei Li

  2. Department of Urology, Hunan Provincial People’s Hospital, the First Affiliated Hospital of Hunan Normal University, Hunan, China

    Xuecheng Wu

  3. College of Basic Medicine, Air Force Medical University, Xi’an, China

    Dongyu Li & Yiwei Liu

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  1. Qi Liang
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Contributions

Qi Liang and Wei Li conceived and designed the project. Xuecheng Wu, Dongyu Li and Yiwei Liu administered the project and developed its methodology. Ruirui Wang, Xiaoying Li and Pengfei Guo analyzed and interpreted the data. Qi Liang wrote the original draft. Wei Li supervised the manuscript and acquired funding. All authors have read and agreed to the published version.

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Correspondence to Wei Li.

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The authors have declared no Competing interest.

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All animal experiments were approved by the Institutional Animal Care and Use Committee, the Third Xiangya Hospital of Central South University (Changsha, China). For experiments using human samples, all samples were anonymously coded following local ethical guidelines (as stipulated by the Declaration of Helsinki). Written informed consent was obtained from patients, and the protocol was approved by the Ethical Review Board of Central South University. All methods were performed in accordance with the relevant guidelines and regulations.

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Liang, Q., Wu, X., Li, D. et al. Dioscin suppresses tumorigenesis and overcomes radioresistance by promoting ubiquitination-mediated degradation of Mcl-1. Cancer Gene Ther (2026). https://doi.org/10.1038/s41417-026-01022-x

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