Pharmacological Research (Nov 2023)

Dietary γ-mangostin triggers immunogenic cell death and activates cGAS signaling in acute myeloid leukemia

  • Zi-Jie Long,
  • Jun-Dan Wang,
  • Sheng-Xiang Qiu,
  • Yi Zhang,
  • Si-Jin Wu,
  • Xin-Xing Lei,
  • Ze-Wei Huang,
  • Jia-Jie Chen,
  • Yong-Liang Yang,
  • Xiang-Zhong Zhang,
  • Quentin Liu

Journal volume & issue
Vol. 197
p. 106973

Abstract

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Immunogenic cell death (ICD), one of cell-death types through release of damage-associated molecular patterns from dying tumor cells, activates tumor-specific immune response and elicits anti-tumor immunity by traditional radiotherapy and chemotherapy. However, whether natural products could induce ICD in leukemia is not elucidated. Here, we report dietary γ-mangostin eradicates murine primary leukemic cells and prolongs the survival of leukemic mice. As well, it restrains primary leukemic cells and CD34+ leukemic progenitor cells from leukemia patients. Strikingly, γ-mangostin attenuates leukemic cells by inducing ICD as characterized by expression of HSP90B1, ANXA1 and IL1B. Additionally, γ-mangostin accelerates cytoplasmic chromatin fragments generation, promoting DNA damage response, and enhances cGAS activation, leading to up-regulation of chemokines. Meanwhile, it induces HDAC4 degradation and acetylated histone H3 accumulation, which promotes chemokines transcription. Ultimately, CD8+ T cell is activated and recruited by γ-mangostin-induced chemokines in the microenvironment. Our study identifies γ-mangostin triggers ICD and activates cGAS signaling through DNA damage response and epigenetic modification. Therefore, dietary γ-mangostin would act as a potential agent to provoke anti-tumor immunity in the prevention and treatment of leukemia.

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