Li Haoyu, Yuan Jianyong, Dong Wei, Yang Cheng, Lu Lihua, Wang Yizhou
Department of Surgery, The First Affiliated Hospital of Naval Medical University Shanghai 200433, The People's Republic of China.
Department of Hepatobiliary Pancreatic Surgery, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine Shanghai 200437, The People's Republic of China.
Am J Transl Res. 2024 Nov 15;16(11):6925-6934. doi: 10.62347/HAEU6139. eCollection 2024.
The mechanism of ferroptosis is primarily driven by the iron-dependent lethal accumulation of membrane lipid peroxidation. Bavachin has been found to exacerbate lipid peroxidation in cancer cells; however, whether it hinders hepatocellular carcinoma (HCC) progression by way of ferroptosis remains unknown.
Cell counting kit-8 (CCK-8) assay was used to measure the effect of Bavachin on the viability of HCC cells, so as to determine the appropriate drug concentration for subsequent experiments. Combining molecular biology experimental techniques such as CCK-8, flow cytometry, western blotting, wound-healing assay, DCFH-DA (2',7'-dichlorodihydrofluorescein diacetate) fluorescent probe and a variety of biological kits, the effects of Bavachin on HCC cell malignant phenotype progression and ferroptosis were investigated.
Bavachin significantly induced cytotoxicity of Huh-7 and HepG2 cells at concentrations of 20 and 40 μM, respectively. Bavachin intervention prominently reduced cell proliferation and migration, and enhanced cell apoptosis in HCC. Also, Bavachin enhanced the process of lipid peroxidation, as indicated by increased reactive oxygen species (ROS), lipid peroxidation (LPO) and malondialdehyde (MDA) production, and decreased superoxide dismutase (SOD) and glutathione (GSH) production. Ferrostin-1, a ferroptosis inhibitor, reduced the Bavachin-induced cell survival rate. Bavachin intervention induced ferroptosis by enhancing iron ion concentration, acyl-CoA synthetase long-chain family member 4 (ACSL4) expression, and reducing glutathione peroxidase-4 (GPX4) expression. Bavachin exerted anti-cancer effects though inducing ferroptosis by activating the nuclear factor erythroid 2-related factor 2 (Nrf2)/Heme oxygenase-1 (HO-1) pathway.
Bavachin acted as a ferroptosis inducer, promoted ROS release, enhanced lipid peroxidation, and inhibited HCC cell malignant phenotype progression by modulating the Nrf2/HO-1 pathway.
铁死亡的机制主要由膜脂质过氧化的铁依赖性致死性积累驱动。已发现补骨脂素会加剧癌细胞中的脂质过氧化；然而，它是否通过铁死亡来阻碍肝细胞癌（HCC）的进展仍不清楚。
使用细胞计数试剂盒-8（CCK-8）测定法来检测补骨脂素对肝癌细胞活力的影响，从而确定后续实验的合适药物浓度。结合CCK-8、流式细胞术、蛋白质免疫印迹法、伤口愈合测定法、DCFH-DA（2',7'-二氯二氢荧光素二乙酸酯）荧光探针等分子生物学实验技术以及多种生物试剂盒，研究补骨脂素对肝癌细胞恶性表型进展和铁死亡的影响。
补骨脂素分别在20和40μM浓度下显著诱导Huh-7和HepG2细胞的细胞毒性。补骨脂素干预显著降低了肝癌细胞的增殖和迁移，并增强了细胞凋亡。此外，补骨脂素增强了脂质过氧化过程，表现为活性氧（ROS）、脂质过氧化（LPO）和丙二醛（MDA）生成增加，超氧化物歧化酶（SOD）和谷胱甘肽（GSH）生成减少。铁死亡抑制剂Ferrostin-1降低了补骨脂素诱导的细胞存活率。补骨脂素干预通过提高铁离子浓度、增强酰基辅酶A合成酶长链家族成员4（ACSL4）表达以及降低谷胱甘肽过氧化物酶4（GPX4）表达来诱导铁死亡。补骨脂素通过激活核因子红细胞2相关因子2（Nrf2）/血红素加氧酶-1（HO-1）途径诱导铁死亡，从而发挥抗癌作用。
补骨脂素作为一种铁死亡诱导剂，通过调节Nrf2/HO-1途径促进ROS释放，增强脂质过氧化，并抑制肝癌细胞恶性表型进展。
