FIN56|1083162-61-1|安捷凯

Background

FIN56, a novel ferroptosis inducer, triggers ferroptosis by increasing the degradation of GPX4 ^[1,4]. FIN56 also activates squalene synthase, an enzyme involved in the cholesterol synthesis ^[2].

FIN56 (0-8.0 μM;24 h) decreased the cell viability of LN229 and U118 cells in a dose-dependent manner. After FIN56 treatment, cell cycle of LN229 and U118 was arrested at GO/G1 phases ^[3]. FIN56 (1-5 μM;3-24 h) induces autophagy-associated cell death in Bladder cancer (BC) cells^[4]. Inhibition of Gpx4 by FIN56 (0-20μM) abolished the protective effects of NAC on HG-induced ferroptosis^[5]. the protein expression of salusin β was upregulated by ferroptosis activators, such as FIN56. Pretreatment with ferrostatin 1 (a ferroptosis inhibitor) prevented the upregulated protein expression of salusin β in HK 2 cells exposed to HG^[6]. AS-IV markedly accelerated proliferation, suppressed apoptosis, and reduced ROS and LDH accumulation. The effects of AS-IV on SCI were inhibited by si-TFEB, and this inhibition was further reinforced by the addition of FIN56(5 μM)^[7].

FIN56 (30days) decreased tumor volume obviously, FIN56 significantly increased protein levels of 4-HNE^[3].

参考文献:
[1]. Shimada K, Skouta R, et,al. Global survey of cell death mechanisms reveals metabolic regulation of ferroptosis. Nat Chem Biol. 2016 Jul;12(7):497-503. doi: 10.1038/nchembio.2079. Epub 2016 May 9. PMID: 27159577; PMCID: PMC4920070.
[2]. Gaschler MM, Andia AA, et,al.FINO2 initiates ferroptosis through GPX4 inactivation and iron oxidation. Nat Chem Biol. 2018 May;14(5):507-515. doi: 10.1038/s41589-018-0031-6. Epub 2018 Apr 2. PMID: 29610484; PMCID: PMC5899674.
[3]. Zhang X, Guo Y, et,al. FIN56, a novel ferroptosis inducer, triggers lysosomal membrane permeabilization in a TFEB-dependent manner in glioblastoma. J Cancer. 2021 Sep 13;12(22):6610-6619. doi: 10.7150/jca.58500. PMID: 34659551; PMCID: PMC8517990.
[4]. Lei P, Bai T, et,al.Mechanisms of Ferroptosis and Relations With Regulated Cell Death: A Review. Front Physiol. 2019 Feb 26;10:139. doi: 10.3389/fphys.2019.00139. PMID: 30863316; PMCID: PMC6399426.
[5]. Li Q, Liao J,et,al. NAC alleviative ferroptosis in diabetic nephropathy via maintaining mitochondrial redox homeostasis through activating SIRT3-SOD2/Gpx4 pathway. Free Radic Biol Med. 2022 Jul;187:158-170. doi: 10.1016/j.freeradbiomed.2022.05.024. Epub 2022 May 31. Erratum in: Free Radic Biol Med. 2022 Aug 20;189:1. PMID: 35660452.
[6].Wang WJ, Jiang X,et,al.Salusin?β participates in high glucose?induced HK?2 cell ferroptosis in a Nrf?2?dependent manner. Mol Med Rep. 2021 Sep;24(3):674. doi: 10.3892/mmr.2021.12313. Epub 2021 Jul 23. PMID: 34296310; PMCID: PMC8335735.
[7]. Zhou Y, Li L, et,al.Astragaloside IV ameliorates spinal cord injury through controlling ferroptosis in H2O2-damaged PC12 cells in vitro. Ann Transl Med. 2022 Nov;10(21):1176. doi: 10.21037/atm-22-5196. PMID: 36467371; PMCID: PMC9708485.

FIN56 是一种新型的铁死亡诱导剂，它通过增加 GPX4 的降解来触发铁死亡 ^[1,4]。 FIN56 还激活角鲨烯合酶，一种参与胆固醇合成的酶^[2]。

FIN56（0-8.0 μM；24 小时）以剂量依赖性方式降低 LN229 和 U118 细胞的细胞活力。 FIN56处理后，LN229和U118的细胞周期停滞在GO/G1期^[3]。 FIN56（1-5 μM；3-24 小时）在膀胱癌 (BC) 细胞中诱导自噬相关细胞死亡^[4]。 FIN56 (0-20μM) 对 Gpx4 的抑制作用消除了 NAC 对 HG 诱导的铁死亡的保护作用^[5]。 salusin β 的蛋白表达被 FIN56 等铁死亡激活剂上调。用 ferrostatin 1（一种铁死亡抑制剂）预处理可防止暴露于 HG^[6] 的 HK 2 细胞中 salusin β 的蛋白表达上调。 AS-IV 显着加速增殖，抑制细胞凋亡，并减少 ROS 和 LDH 积累。 AS-IV 对 SCI 的影响被 si-TFEB 抑制，并且这种抑制通过添加 FIN56(5 μM)^[7] 得到进一步加强。

FIN56（30天）明显缩小肿瘤体积，FIN56显着增加4-HNE蛋白水平^[3]。

Protocol

Cell experiment [1]:

Cell lines

LN229 and U118 GBM cell lines

Preparation Method

Cells were plated into 96-well plates and incubated overnight. Different doses of FIN56 (0, 0.1, 0.5, 1.0, 2.0 4.0 and 8.0 μM) was added to wells. 24 h later, CCK-8 solution was added to each well. 2 h later, samples were measured at 450 nm on a microplate reader.

Reaction Conditions

FIN56 (0-8.0 μM);24 h

Applications

FIN56 decreased the cell viability of LN229 and U118 cells in a dose-dependent manner.

Animal experiment [2]:

Animal models

Nude mouse model

Preparation Method

LN229 cells were injected subcutaneously into the right shoulder of 4-week-old nude mice. 2 weeks later, nude mice (n = 10) were divided into two groups, control group and FIN56 treatment group. Subcutaneous tumors were harvested 30 days after treatment.

Dosage form

30 days

Applications

FIN56 decreased tumor volume obviously, FIN56 significantly increased protein levels of 4-HNE.

参考文献:

[1]. Zhang X, Guo Y, et,al. FIN56, a novel ferroptosis inducer, triggers lysosomal membrane permeabilization in a TFEB-dependent manner in glioblastoma. J Cancer. 2021 Sep 13;12(22):6610-6619. doi: 10.7150/jca.58500. PMID: 34659551; PMCID: PMC8517990.

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