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

Cell Chemical Biology
Yan ZhangBrent R Stockwell

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.

Citations

Oct 9, 2019·Advanced Materials·Chen LiangXiaochen Dong
Oct 22, 2019·Nature·Kirill BersukerJames A Olzmann
Mar 4, 2020·International Journal of Molecular Sciences·Ricardo U Macías-RodríguezFrancisco Javier Cubero
Aug 18, 2020·Autophagy·Xin ChenDaolin Tang
Feb 6, 2020·Cancers·Marta Obara-Michlewska, Monika Szeliga
Apr 4, 2020·Science·Michael A BadgleyKenneth P Olive
May 28, 2020·Frontiers in Oncology·Boutaina DaherJacques Pouysségur
Aug 21, 2020·Nature·Jessalyn M UbellackerSean J Morrison
Aug 12, 2020·Journal of Hematology & Oncology·Rong TangSi Shi
Oct 16, 2019·Proceedings of the National Academy of Sciences of the United States of America·Alexia BelavgeniAndreas Linkermann
Feb 8, 2020·Nature Cell Biology·Hyemin LeeBoyi Gan
Apr 5, 2020·International Journal of Molecular Sciences·Uris RosAna J Garcia-Saez
Sep 11, 2020·Oxidative Medicine and Cellular Longevity·Yani WangJinwei Tian
May 19, 2019·Nature Reviews. Cancer·José Pedro Friedmann AngeliMarcus Conrad
Nov 20, 2019·Nature Chemical Biology·Marcus Conrad, Derek A Pratt
Dec 4, 2019·Annals of the New York Academy of Sciences·Jennifer CableWilliam Kaelin
Feb 9, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Jie LiuDongfeng Chen
Jan 16, 2020·Cancers·Christina M BebberSilvia von Karstedt
Feb 23, 2020·Nature Chemical Biology·Alexandr A KapralovValerian E Kagan
Jul 2, 2020·OncoTargets and Therapy·Yuechen ZhaoYan Jiao
Oct 21, 2020·Archives of Pharmacal Research·Kyu Min KimSung Hwan Ki
Nov 25, 2020·Proceedings of the National Academy of Sciences of the United States of America·Junmei YiXuejun Jiang
Dec 29, 2020·Cell Metabolism·Yun Pyo KangGina M DeNicola
Dec 30, 2020·Biochemical and Biophysical Research Communications·Nanjun HuDaolin Tang
Jan 25, 2021·Neuroscience Letters·Min-Yi YaoJing Gao
Jan 27, 2021·Nature Reviews. Molecular Cell Biology·Xuejun JiangMarcus Conrad
Sep 23, 2020·Trends in Molecular Medicine·Marcus ConradBettina Proneth
Feb 4, 2021·The International Journal of Neuroscience·Thomas M Berry, Ahmed A Moustafa
Feb 5, 2021·Cell Chemical Biology·Feimei KuangRui Kang
Feb 7, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Ning LiQing Geng
Feb 9, 2021·Frontiers in Cell and Developmental Biology·Xin ChenRui Kang
Jan 31, 2021·Nature Reviews. Clinical Oncology·Xin ChenDaolin Tang
Feb 5, 2021·Signal Transduction and Targeted Therapy·Hong-Fa YanPeng Lei
Dec 10, 2020·Oxidative Medicine and Cellular Longevity·Xiang WeiDing-Sheng Jiang
Jan 7, 2021·Autophagy·Jingbo LiDaolin Tang
Jan 30, 2021·Nature Communications·Jiao LiuDaolin Tang
Mar 12, 2020·Cell Reports·Huizhong FengBrent R Stockwell
Apr 11, 2020·Cell Chemical Biology·Hülya BayırValerian E Kagan
Apr 16, 2020·Cell Chemical Biology·Brent R Stockwell, Xuejun Jiang

❮ Previous
Next ❯

Related Concepts

Related Feeds

B-Cell Lymphoma

B-cell lymphomas include lymphomas that affect B cells. This subtype of cancer accounts for over 80% of non-Hodgkin lymphomas in the US. Here is the latest research.