Imidazole ketone erastin induces ferroptosis and slows tumor growth in a mouse lymphoma model
By Yan Zhang, Hui-Li Tan, Jacob D Daniels, Fereshteh Zandkarimi, Hengrui Liu, L. Brown, K. Uchida, O. O'Connor, Brent R. Stockwell. Cell Chemical Biology, 2019
650 citations recorded by the source corpus.
SUMMARY 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 pharmacokinetics and pharmacodynamics for 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 quantitative PCR (qPCR), we identified distinct features of lipid metabolism in IKE-induced ferroptosis. In addition, biodegradable polyethylene glycol-poly(lactic-co-glycolic acid) nanoparticles (PEG-PLGA NPs) were employed to aid in IKE delivery and exhibited reduced toxicity compared to free IKE in a DBLCL xenograft model.
Subfields: Cancer Research, Molecular Biology, Pulmonary and Respiratory Medicine
View Paper: https://www.semanticscholar.org/paper/317d635b3d05f00cdbf30a970b87ae20b98d9686
How researchers see this paper
The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.
In Cancer Research
- Brent R. Stockwell
- Xuejun Jiang
- Jiajun Zhu
- Qing-zhang Tuo
- P. Lei
- W. Gu
- Craig B. Thompson
- M. V. Vander Heiden
In Molecular Biology
In Pulmonary and Respiratory Medicine
Citations in the corpus
- The cell biology of ferroptosis (2024, neutral): “However, increased levels of the DNA-damage marker 8-oxo-2′-deoxyguanosine (8-oxo-dG) can correlate with the induction of ferroptosis in vivo 163 .”
- Ferroptosis in cancer: from molecular mechanisms to therapeutic strategies (2024, methodology): “Current models mainly rely on the use of FINs, such as IKE and cyst(e)inase, 43,53,192,465,496 to treat xenograft tumors.”
- Emerging mechanisms and disease relevance of ferroptosis (2020, background): “Indeed, tumor xenograft experiments in mice using an erastin derivative with better pharmacological properties, imidazole ketone erastin (IKE), showed a clear therapeutic benefit without causing significant weight loss of mice, which is a general sign of toxicity [86,95]; this suggests that IKE will”
- Oncogenic activation of PI3K-AKT-mTOR signaling suppresses ferroptosis via SREBP-mediated lipogenesis (2020, methodology): “In the other mouse model, we used imidazole ketone erastin (IKE), a potent and metabolically stable analog of erastin that has been validated for in vivo use (39), instead of genetic deletion of GPX4, to induce tumor cell ferroptosis.”
- Transferrin Receptor Is a Specific Ferroptosis Marker (2020, methodology): “…(D64E10) XP Rabbit mAb Cell Signaling Technology Cat# 5625, RRID:AB_10699459 Biological Samples B cell lymphoma mouse xenograft model Reference (Zhang et al., 2019) N/A Hepatocellular carcinoma (HCC) mouse xenograft model Brent R. Stockwell lab N/A Murine glioma model Peter D. Canoll lab…”