Erastin

Erastin is a ferroptosis inducer. Erastin exhibits the mechanism of ferroptosis induction related to ROS and iron-dependent signaling. Erastin inhibits voltage-dependent anion channels (VDAC2/VDAC3) and accelerates oxidation, leading to the accumulation of endogenous reactive oxygen species. Erastin also disrupts mitochondrial permeability transition pore (mPTP) with anti-tumor activity. Furthermore, Erastin can block the uptake of cystine mediated by SLC7A11 and also spares UMRC6-EV and -C91A cells from disulfidptosis under glucose starvation^{[1][2][3][4][5][6][7][8][9][10][11][12][13][14]}. In Vitro:Erastin (10 μM; 24 h) triggers ferroptosis in ectopic endometrial stromal cells (EESCs), and increases the total ROS level at 9 h^[1].
Erastin shorts mitochondria and increases membrane density in EESCs^[1].
Erastin (10 μM; 9 h) decreases the mRNA expression levels of iron-related proteins, such FPN (iron exporter) in EESCs. However, FPN overexpression significantly inhibits erastin-induced ferroptosis in EESCs^[1].
Erastin (10 μM; 24 h) induces mitochondrial permeability transition pore (mPTP) opening in HT-29 colorectal cancer cells^[2].
Erastin (30 μM; 72 h) significantly inhibits the growth of HT-29 colorectal cancer cells^[2].
The molecular mechanism by which Erastin induces ferroptosis is related to genes regulating iron or mitochondrial fatty acid metabolism. Includes ribosomal protein L8, iron response element binding protein 2 (IREB2), ATP synthase F0 complex subunit C3, citrate synthase, tetrapeptide repeat domain 35, and acyl-CoA synthetase family member 2 (ACSF2)^[3].
Note:
1. Different cell lines may have different sensitivity to a same compound. As reported, A549, HCT116, HepG2, H1299 cells may be insensitive to Erastin^[3][4][5].
2. Erastin is unstable in solution. Freshly prepared is recommended.

Ferroptosis-sensitive Cell Lines

Ferroptosis-sensitive Cells	Test Conditions
SKOV3[6]	5-20 μM; 1-7 days
OVCA429[6]	5-20 μM; 1-7 days
MCF10A-RAS[7]	0-30 μM; 48 h
HT-22 neuron[8]	500 nM; 16 h
NCI-H508[9]	0.1-10 μM; 48 h
LoVo[9]	0.1-10 μM; 48 h
LS513[9]	0.1-10 μM; 48 h
SW480[9]	0.1-10 μM; 48 h
SW620[9]	0.1-10 μM; 48 h
SW1116[9]	0.1-10 μM; 48 h
DLD-1[9]	0.1-10 μM; 48 h
Caco-2[9]	0.1-10 μM; 48 h
SW837[10]	0-40 μM; 24 h
Pfa1[11]	0.1-5 μM; 48 h
HT-1080[12]	0.1-5 μM; 48 h
MAD-MB-231[13]	0-100 μM; 72 h; IC50: 9.55 μM
HCC1937[13]	0-100 μM; 72 h; IC50: 11.58 μM

Ferroptosis-insensitive Cell Lines

Ferroptosis-insensitive Cells	Test Conditions
HCT116[11]	0-40 μM; 24 h
SW48[11]	0-40 μM; 24 h
HepG2[5]	0-20 μM; 24 h
MDA-MB-436[13]	0.1-25 μM; 24 h
HT-29[13]	0.1-25 μM; 24 h
U-373[13]	0.1-25 μM; 24 h

In Vivo:Erastin can be used in animal modeling to construct ferroptosis induction model.

Erastin (40 mg/kg; i.p.; once every 3 days for 2 weeks) suppresses endometriotic implants in the mouse endometriosis model, indicating Erastin regresses ectopic lesions by trigging ferroptosis^[1].
Erastin (10 mg/kg, 30 mg/kg; i.p.; once daily for 4 weeks) suppresses HT-29 xenograft growth in SCID mice, with more potent efficacy under 30 mg/kg treatment^[2].