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18β-glycyrrhetinic acid suppresses Lewis lung cancer growth through protecting immune cells from ferroptosis

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Abstract

Purpose

18β-glycyrrhetinic acid (GA), the main metabolite of glycyrrhizic acid extracted from the root of licorice, has been reported to possess anti-cancer and immunomodulatory activity, but the mechanisms are not well understood. Recent studies have shown that ferroptosis of immune cells is involved in tumor-associated immune suppression. The purpose of this study was to investigate whether the enhanced immune response via inhibiting immune cell ferroptosis contributed to the anticancer effect of 18β-GA.

Methods

Lewis Lung carcinoma mouse model and Murine CD8 + T cell culture model were used to examine the changes of immune response and ferroptosis of immune cells.

Results

We found that 18β-GA was effective against lung cancer accompanied by enhanced activation of tumor-infiltrating CD8+ T cells in Lewis Lung carcinoma mouse model. Furthermore, we demonstrated that the boosted immune response by GA was attributed to its ability to inhibit arachidonic acid (AA)-mediated CD8+ T ferroptosis via suppressing CD36 expression.

Conclusion

The findings of the present study unraveled a novel mechanism underlying the anti-cancer and immunomodulatory activity of 18β-GA and support that 18β-GA holds potential to be used as an immune enhancer for lung cancer prevention or treatment.

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Data availability

Data will be made available on reasonable request.

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Acknowledgements

This research was supported by the Ministry of Science and Technology of China [National Key Research and Development Program of China, 2023YFF1105202].

Funding

National Key Research and Development Program of China, 2018YFC1603706, Hongbo Hu.

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Authors and Affiliations

  1. College of Food Science and Nutritional Engineering, China Agricultural University, No.17 Qinghua East Road, Haidian District, Beijing, 100083, China

    Xuan Ma, Zhenou Sun, Hui Chen, Lixing Cao, Shuang Zhao, Chong Zhao, Shutao Yin & Hongbo Hu

  2. College of Veterinary Medicine, China Agricultural University, No.2 Yunamingyuan West Road, Haidian District, Beijing, 100193, China

    Lihong Fan

  3. College of Biochemical Engineering, Beijing Union University, Beijing, China

    Xuan Ma

  4. College of Food Science and Nutritional Engineering, Tianjin University of Science and Technology, Tianjin, China

    Zhenou Sun

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  1. Xuan Ma
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Correspondence to Lihong Fan or Hongbo Hu.

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Ma, X., Sun, Z., Chen, H. et al. 18β-glycyrrhetinic acid suppresses Lewis lung cancer growth through protecting immune cells from ferroptosis. Cancer Chemother Pharmacol (2024). https://doi.org/10.1007/s00280-024-04639-7

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