β-Mangostin targets and suppresses glioma via STING activation and tumor-associated microglia polarization - 23/07/24

Doi : 10.1016/j.biopha.2024.117074

Yimin Yang ^a,^{^{1
Joint first authorship.}}, Xuling Luo ^a,^{^{1
Joint first authorship.}}, Yaling Wang ^b,^{^{1
Joint first authorship.}}, Aibo Xu ^b, Lina Peng ^b, Xiaoting Zhang ^a, Zhen Wang ^b,^c,^⁎ , Youmin Ying ^a,^⁎ , Kaiqiang Li ^b,^c,^⁎
^a College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou, Zhejiang 310014, China
^b Center for Laboratory Medicine, Allergy center, Department of Transfusion medicine, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang 310014, China
^c Key Laboratory of Biomarkers and In Vitro Diagnosis Translation of Zhejiang Province, Hangzhou, Zhejiang 310063, China

^⁎Corresponding author.^⁎⁎Corresponding author at: Center for Laboratory Medicine, Allergy center, Department of Transfusion medicine, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang 310014, China.Center for Laboratory Medicine, Allergy center, Department of Transfusion medicine, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical CollegeHangzhouZhejiang310014China

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.

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Abbreviations : Arg-1, AST, ALT, ELISA, GCM, Iba-1, IL-1β, IL-4, IL-6, IL-10, INOS, PBS, SPR, MCM, MM-PBSA, MMP-2, MMP-9, STING, TBK1, TP, β-mgs

Keywords : Mangosteen, Xanthone, Stimulator of interferon genes, Anti-PD-1 antibody, Immunosuppressive microenvironment, Biosafety

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Vol 177

Article 117074- août 2024 Retour au numéro

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β-Mangostin targets and suppresses glioma via STING activation and tumor-associated microglia polarization - 23/07/24

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