Department of Thoracic Surgery, The Third Affiliated Hospital of Chongqing Medical University, Chongqing 401120, China.
Dis Markers. 2022 Oct 11;2022:4607966. doi: 10.1155/2022/4607966. eCollection 2022.
Ferroptosis is an iron- and ROS-dependent form of cell death initiated by lipid peroxidation. The rapidly developing study of ferroptosis has facilitated its application in cancer therapeutics. The current study is aimed at investigating the functional property of ferulic acid (FA, a phenolic acid substance) on inducing ferroptosis in antiesophageal squamous cell carcinoma (ESCC).
ESCC cells were administrated with gradient doses of FA or with ferroptosis inhibitor deferoxamine. Cellular growth was measured with CCK-8 and colony formation experiments. LDH, caspase-3, MDA, SOD, GSH, and iron were assayed with corresponding kits. Apoptotic level was evaluated through Annexin V-FITC apoptosis staining, with migration and invasion utilizing Transwell assays. Through quantitative RT-PCR, angiogenesis-relevant genes VEGFA and PDGFB were detected. ROS generation was measured via DCFH-DA probe. Immunoblotting was conducted for monitoring ACSL4, SLC7A11, HO-1, and GPX4.
FA administration observably mitigated cellular viability and colony formation capacity and motivated LDH release, caspase-3 activity, and apoptosis in EC-1 and TE-4 cells. In addition, migration and invasion together with angiogenesis of ESCC cells were restraint by FA. FA exposure led to the increase of MDA content, ROS production, and iron load as well as the reduction of SOD activity and GSH content. Also, FA augmented the activities of ACSL4 and HO-1, with lessening SLC7A11 and GPX4. Nonetheless, deferoxamine restrained the effect of FA on ESCC ferroptosis.
Altogether, FA may act as a ferroptosis inducer and thus attenuates cell growth and invasion of ESCC, which boosts the clinical application of FA in ESCC therapeutics.
铁死亡是一种由脂质过氧化引发的、依赖铁和 ROS 的细胞死亡形式。铁死亡研究的迅速发展促进了其在癌症治疗中的应用。本研究旨在研究阿魏酸（FA，一种酚酸物质）在诱导抗食管鳞状细胞癌（ESCC）铁死亡中的功能特性。
用梯度剂量的 FA 或铁死亡抑制剂去铁胺处理 ESCC 细胞。用 CCK-8 和集落形成实验测量细胞生长。用相应的试剂盒测定 LDH、caspase-3、MDA、SOD、GSH 和铁。通过 Annexin V-FITC 凋亡染色评估凋亡水平，通过 Transwell 测定迁移和侵袭。通过定量 RT-PCR 检测血管生成相关基因 VEGFA 和 PDGFB。通过 DCFH-DA 探针测量 ROS 生成。通过免疫印迹监测 ACSL4、SLC7A11、HO-1 和 GPX4。
FA 处理明显减轻了 EC-1 和 TE-4 细胞的细胞活力和集落形成能力，并促进了 LDH 释放、caspase-3 活性和细胞凋亡。此外，FA 抑制了 ESCC 细胞的迁移和侵袭以及血管生成。FA 暴露导致 MDA 含量、ROS 产生和铁负荷增加，SOD 活性和 GSH 含量降低。此外，FA 增强了 ACSL4 和 HO-1 的活性，降低了 SLC7A11 和 GPX4 的活性。然而，去铁胺抑制了 FA 对 ESCC 铁死亡的作用。
总之，FA 可能作为一种铁死亡诱导剂，从而减弱 ESCC 的细胞生长和侵袭，这增加了 FA 在 ESCC 治疗中的临床应用。
