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.
Keywords: 18β-glycyrrhetinic acid; CD36; Ferroptosis; Immune response; Lung cancer.
© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.