%0 Journal Article
%T Artesunate induces melanoma cell ferroptosis and augments antitumor immunity through targeting Ido1.
%A Liu W
%A Zhou H
%A Lai W
%A Hu C
%A Wang Q
%A Yuan C
%A Luo C
%A Yang M
%A Hu M
%A Zhang R
%A Li G
%J Cell Commun Signal
%V 22
%N 1
%D 2024 Jul 26
%M 39061097
%F 7.525
%R 10.1186/s12964-024-01759-8
%X 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.