Cell Communication and Signaling (Jul 2024)

Artesunate induces melanoma cell ferroptosis and augments antitumor immunity through targeting Ido1

  • Wuyi Liu,
  • Huyue Zhou,
  • Wenjing Lai,
  • Changpeng Hu,
  • Qiaoling Wang,
  • Chengsha Yuan,
  • Chunmei Luo,
  • Mengmeng Yang,
  • Min Hu,
  • Rong Zhang,
  • Guobing Li

DOI
https://doi.org/10.1186/s12964-024-01759-8
Journal volume & issue
Vol. 22, no. 1
pp. 1 – 17

Abstract

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Abstract Artesunate (ART), a natural product isolated from traditional Chinese plant Artemisia annua, has not been extensively explored for its anti-melanoma properties. In our study, we found that ART inhibited melanoma cell proliferation and induced melanoma cell ferroptosis. Mechanistic study revealed that ART directly targets Ido1, thereby suppressing Hic1-mediated transcription suppression of Hmox1, resulting in melanoma cell ferroptosis. In CD8+ T cells, ART does not cause cell ferroptosis due to the low expression of Hmox1. It also targets Ido1, elevating tryptophan levels, which inhibits NFATc1-mediated PD1 transcription, consequently activating CD8+ T cells. Our study uncovered a potent and synergistic anti-melanoma efficacy arising from ART-induced melanoma cell ferroptosis and concurrently enhancing CD8+ T cell-mediated immune response both in vivo and in vitro through directly targeting Ido1. Our study provides a novel mechanistic basis for the utilization of ART as an Ido1 inhibitor and application in clinical melanoma treatment.

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