Erastin is a cell-permeable ferroptosis activatior and an antitumor agent that is selective for cell expressing oncogene RAS.
Erastin induces ferroptosis through directly binding to VDAC2/3 to alter the permeability of the outer mitochondrial membrane, which decreases the rate of NADH oxidation. Besides exerting targeted effects, erastin also enhances chemotherapy, targeted therapy, and immunotherapy in certain cancer cells, suggesting a potential role of erastin in cancer cell treatment.[3]
Erastin and its analogs specifically inhibited cystine uptake via system xc−, and triggered ferroptosis in a variety of cellular contexts and act much more potently than SAS. Moreover, Erastin was ∼2500 times more potent than SAS as an inhibitor of system xc− function in both HT-1080 and Calu-1 cells (HT-1080: erastin IC50 = 0.20 µM, SAS IC50 = 450 µM; Calu-1: erastin IC50 = 0.14 µM, SAS IC50 = 460 µM).[1]
Erastin, an inhibitor of SLC7A11, was found to hold a remarkably stronger cytotoxic effect on colorectal CSCs via in vitro and in vivo experiments. Besides, Erastin attenuated the chemoresistance of colorectal CSCs (colorectal cancer stem cells). For in vivo experiment, Erastin (10 mg/kg) was intravenously injected into mice with colorectal cancer every two days. It was found that Erastin inhibited ALDH1 activity, and reduced sphere size and number in colorectal cancer cells. [2]
References:
[1]. Dixon SJ, et al. Pharmacological inhibition of cystine-glutamate exchange induces endoplasmic reticulum stress and ferroptosis. Elife. 2014 May 20;3:e02523.
[2]. Xu X, et al. Targeting SLC7A11 specifically suppresses the progression of colorectal cancer stem cells via inducing ferroptosis. Eur J Pharm Sci. 2020 Sep 1;152:105450.
[3]. Yang Y, et al. Nedd4 ubiquitylates VDAC2/3 to suppress erastin-induced ferroptosis in melanoma. Nat Commun. 2020 Jan 23;11(1):433.
Erastin是一种能够穿透细胞膜的铁死亡激活剂和抗肿瘤药物，它选择性地作用于表达癌基因RAS的细胞。
Erastin通过直接结合VDAC2/3改变外线粒体膜的渗透性，从而诱导铁死亡，并降低NADH氧化速率。除了产生针对性效果外，erastin还可以增强某些癌细胞的化疗、靶向治疗和免疫治疗效果，表明erastin在癌细胞治疗中具有潜在作用。[3]
Erastin及其类似物通过系统xc-特异性抑制半胱氨酸的摄取，并在各种细胞环境中触发铁死亡，比SAS更具有强大的作用。此外，在HT-1080和Calu-1细胞中，Erastin对于系统xc-功能的抑制作用约为SAS的2500倍（HT-1080：erastin IC50 = 0.20 µM，SAS IC50 = 450 µM；Calu-1：erastin IC50 = 0.14 µM，SAS IC50 = 460 µM）。
通过体内外实验，发现抑制SLC7A11的Erastin对结肠癌干细胞具有更强的细胞毒性作用。此外，Erastin还减轻了结肠癌干细胞（即结肠癌干细胞）对化疗药物的耐药性。在体内实验中，将Erastin（10mg/kg）每两天静脉注射到患有结肠癌的小鼠体内。结果发现，Erastin抑制了ALDH1活性，并减少了结肠癌细胞球大小和数量。[2]