β-Mangostin targets and suppresses glioma via STING activation and tumor-associated microglia polarization

Abstract

Glioma, a common and highly malignant central nervous system tumor, markedly influences patient prognosis via interactions with glioma-associated macrophages. Previous research has revealed the anticancer potential of β-mangostin, a xanthone derivative obtained from the mangosteen fruit. This research investigated the role of β-mangostin on microglia in the glioma microenvironment and evaluated the efficacy of β-mangostin combined with anti-PD-1 antibody (αPD-1) in glioma-bearing mice. The results showed that, β-mangostin attenuated M2 polarization in BV2 cells and promoted M1-related interleukin (IL)-1β and IL-6 secretion, thereby inhibiting glioma invasion. In addition, β-mangostin improved the anti-glioma effects of αPD-1 and increased CD8+T cell and M1-type microglia infiltration. Mechanistically, β-mangostin bound to the stimulator of interferon genes (STING) protein, which is crucial for the anti-tumor innate immune response, and promoted STING phosphorylation in microglia, both in vivo and in vitro. These results provide insights into its mode of action and supporting further investigation into β-mangostin as a therapeutic agent.

Keywords

• Mangosteen
• Xanthone
• Stimulator of interferon genes
• Anti-PD-1 antibody
• Immunosuppressive microenvironment
• Biosafety