Artesunate induces ER-derived-ROS-mediated cell death by disrupting labile iron pool and iron redistribution in hepatocellular carcinoma cells.

ABSTRACT: Aberrant iron homeostasis is a typical characteristic of Hepatocellular carcinoma (HCC), and perturbation of iron metabolism is an effective strategy for HCC therapy. However, there are few safe and effective targeting agents available in clinical practices. The artemisinin and its derivatives have shown potential anti-cancer activity by disturbing cellular iron homeostasis, but the specific mechanism is still unclear. In this study, we demonstrate that Artesunate (ART), a water-soluble anti-malaria agent in clinical use, can regulate the labile iron pool (LIP) and effectively induce ROS-dependent cell death in multiple HCC cells. Mechanistically, ART increases the LIP by promoting lysosomal degradation of iron-storage protein ferritin through acidizing lysosomes. Then the accumulation of

SUBMITTER: Jiang Z 

PROVIDER: S-EPMC7994160 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature