Erastin

Erastin is a ferroptosis activator. Erastin inhibits system Xc- to reduce intracellular glutathione levels and weaken GPX4 activity. Erastin binds VDAC2/3 to promote mitochondrial dysfunction and excessive reactive oxygen species production, thereby inducing ferroptosis in tumor cells. Erastin can be used for research on cancer, neurodegenerative diseases and ischemia-reperfusion injury^[1-4].

In vitro, treatment of HeLa and NCI-H1975 cells with 0.1-50μM Erastin for 24 hours dose-dependently reduced cell viability, downregulated GPX4 protein expression, and decreased intracellular total glutathione and GSH concentrations^[5]. Treatment of Tu177 cells and FaDu cells with 10μM Erastin for 24-72 hours reduced cell viability and colony formation ability, weakened cell invasion and migration ability, and increased Fe²⁺ and malondialdehyde content^[6]. Treatment of HT-29, DLD-1 and Caco-2 cells with 0.1-30μM Erastin for 48 hours reduced cell survival rate and colony formation number, increased dead cell proportion, and increased intracellular reactive oxygen species levels^[7].

In vivo, daily intraperitoneal injection of 40mg/kg Erastin for 2 weeks in immunodeficient nude mice subcutaneously implanted with BECN1-overexpressing cells inhibited subcutaneous tumor growth and reduced final tumor volume, increased intratumoral malondialdehyde levels, and decreased intratumoral glutathione levels^[8]. Intraperitoneal injection of 40mg/kg Erastin daily or every other day from day 14 for 14 days in a C57BL/6 mouse model of endometriosis receiving 30μg/kg 17-β-estradiol benzoate every 3 days for 28 days reduced ectopic endometriotic lesion volume^[9]. Intraperitoneal injection of 20mg/kg Erastin every other day for 2 weeks in BALB/c-nu mice subcutaneously implanted with SK-OV-3 cells inhibited subcutaneous tumor growth and reduced final tumor volume and weight, decreased intratumoral Ki67-positive cell proportion, and decreased intratumoral GPX4 protein expression^[10].

References:

[1] Zhao Y, Li Y, Zhang R, et al. The Role of Erastin in Ferroptosis and Its Prospects in Cancer Therapy. Onco Targets Ther. 2020 Jun 11;13:5429-5441.

[2] Koppula P, Zhuang L, Gan B. Cystine transporter SLC7A11/xCT in cancer: ferroptosis, nutrient dependency, and cancer therapy. Protein Cell. 2021 Aug;12(8):599-620.

[3] Gao Z, Du J. Erastin-induced multi-pathway cell death in endometriosis: a mechanistic and translational narrative review. Front Med (Lausanne). 2025 Sep 10;12:1594702.

[4] Gan B. How erastin assassinates cells by ferroptosis revealed. Protein Cell. 2023 Mar 16;14(2):84-86.

[5] Shibata Y, Yasui H, Higashikawa K, et al. Erastin, a ferroptosis-inducing agent, sensitized cancer cells to X-ray irradiation via glutathione starvation in vitro and in vivo. PLoS ONE. 2019 Dec 4;14(12):e0225931.

[6] Wu X, Wu J. A polo-like kinase 1 inhibitor enhances erastin sensitivity in head and neck squamous cell carcinoma cells in vitro. Cancer Chemother Pharmacol. 2024;94:183-195.

[7] Huo H, Zhou Z, Qin J, et al. Erastin Disrupts Mitochondrial Permeability Transition Pore (mPTP) and Induces Apoptotic Death of Colorectal Cancer Cells. PLoS ONE. 2016 May 12;11(5):e0154605.

[8] Song X, Zhu S, Chen P, et al. AMPK-mediated BECN1 phosphorylation promotes ferroptosis by directly blocking system Xc- activity. Curr Biol. 2018 Aug 6;28(15):2388-2399.e5.

[9] Li Y, Zeng X, Lu D, et al. Erastin induces ferroptosis via ferroportin-mediated iron accumulation in endometriosis. Hum Reprod. 2021 Apr;36(4):951-964.

[10] Li W, Ji T, Ye J, et al. Ferroptosis enhances the therapeutic potential of oncolytic adenoviruses KD01 against cancer. Cancer Gene Ther. 2025;32:403-417.