Imidazole Ketone Erastin Induces Ferroptosis and Slows Tumor Growth in a Mouse Lymphoma Model.

ABSTRACT: Ferroptosis is a form of regulated cell death that can be induced by inhibition of the cystine-glutamate antiporter, system x_c^-. Among the existing system x_c^- inhibitors, imidazole ketone erastin (IKE) is a potent, metabolically stable inhibitor of system x_c^- and inducer of ferroptosis potentially suitable for in vivo applications. We investigated the pharmacokinetic and pharmacodynamic features of IKE in a diffuse large B cell lymphoma (DLBCL) xenograft model and demonstrated that IKE exerted an antitumor effect by inhibiting system x_c^-, leading to glutathione depletion, lipid peroxidation, and the induction of ferroptosis biomarkers both in vitro and in vivo. Using untargeted lipidomics and qPCR, we i

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC6525071 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature