Metabolomics

Dataset Information

0

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 xc-. Among the existing system xc- inhibitors, imidazole ketone erastin (IKE) is a potent, metabolically stable inhibitor of system xc- 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 xc-, leading to glutathione depletion, lipid peroxidation, and the induction of ferroptosis biomarkers both in vitro and in vivo. Using untargeted lipidomics and qPCR, we identified distinct features of lipid metabolism in IKE-induced ferroptosis. In addition, biodegradable polyethylene glycol-poly(lactic-co-glycolic acid) nanoparticles were employed to aid in IKE delivery and exhibited reduced toxicity compared with free IKE in a DLBCL xenograft model.

INSTRUMENT(S): Liquid Chromatography MS - Negative (LC-MS (Negative)), Liquid Chromatography MS - Positive (LC-MS (Positive))

SUBMITTER: Fereshteh Zandkarimi 

PROVIDER: MTBLS774 | MetaboLights | 2019-04-17

REPOSITORIES: MetaboLights

altmetric image

Publications

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

Zhang Yan Y   Tan Hui H   Daniels Jacob D JD   Zandkarimi Fereshteh F   Liu Hengrui H   Brown Lewis M LM   Uchida Koji K   O'Connor Owen A OA   Stockwell Brent R BR  

Cell chemical biology 20190221 5


Ferroptosis is a form of regulated cell death that can be induced by inhibition of the cystine-glutamate antiporter, system x<sub>c</sub><sup>-</sup>. Among the existing system x<sub>c</sub><sup>-</sup> inhibitors, imidazole ketone erastin (IKE) is a potent, metabolically stable inhibitor of system x<sub>c</sub><sup>-</sup> 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 ly  ...[more]

Similar Datasets

2020-03-10 | PXD017425 | Pride
2020-09-16 | GSE148297 | GEO
2023-06-19 | GSE234894 | GEO
2023-09-19 | GSE242976 | GEO
2023-10-11 | GSE189822 | GEO
2023-10-11 | GSE218284 | GEO
2024-10-31 | GSE273622 | GEO
2024-06-20 | GSE269789 | GEO
2024-06-20 | GSE269788 | GEO
2024-06-11 | GSE238147 | GEO