ATF3 promotes ferroptosis in sorafenib-induced cardiotoxicity by suppressing Slc7a11 expression.

ABSTRACT: Sorafenib is the unique recommended molecular-targeted drug for advanced hepatocellular carcinoma, but its clinical use is limited due to cardiotoxicity. As sorafenib is an efficient ferroptosis inducer, the pathogenesis of this compound to ferroptosis-mediated cardiotoxicity is worth further study. Mice were administered 30 mg/kg sorafenib intraperitoneally for 2 weeks to induce cardiac dysfunction and Ferrostatin-1 (Fer-1) was used to reduce ferroptosis of mice with sorafenib-induced cardiotoxicity. Sorafenib reduced levels of anti-ferroptotic markers involving Slc7a11 and glutathione peroxidase 4 (GPX4), increased malonaldehyde malondialdehyde, apart from causing obvious mitochondria damage, which was alleviated by Fer-1. In vitro experiments showed that Fer-1 inhibited lipid per

SUBMITTER: Li Y 

PROVIDER: S-EPMC9537618 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature