Erastin is a ferroptosis activator.

Erastin triggers oxidative, iron-dependent cell death. Treatment of NRAS-mutant HT-1080 fibrosarcoma cells with the RSL molecule erastin (10 µM) results in a time-dependent increase in cytosolic and lipid ROS beginning at 2 hours^[1]. Cell death triggered by erastin is significantly inhibited by antioxidants (e.g., α-tocopherol, butylated hydroxytoluene, and β-carotene) and iron chelators (e.g., deferoxamine), suggesting that ROS- and iron-dependent signaling is required for erastin-induced ferroptosis. Erastin can directly bind to VDAC2/3 in BJeLR cells. Knockdown of VDAC2 and VDAC3, but not VDAC1, leads to erastin resistance. Erastin has the ability to reduce glutathione level by directly inhibiting cystine/glutamate antiporter system Xc− activity, with activation of the ER stress response^[2]. Erastin potently inhibits HT-29 cell survival. Erastin shows a dose-dependent effect, and 30 μM of erastin displays the most dramatic effect^[3].

Intraperitoneal injection of erastin at well-tolerated doses dramatically inhibits HT-29 xenograft growth in severe combined immunodeficient mice^[3].

• [1]. Dixon SJ, et al. Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell. 2012 May 25;149(5):1060-72.

  [2]. Xie Y, et al. Ferroptosis: process and function. Cell Death Differ. 2016 Mar;23(3):369-79.

  [3]. Huo H, 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.