Engineering Research Centre of Molecular Medicine, Ministry of Education, Fujian Key Laboratory of Molecular Medicine, Key Laboratory of Precision Medicine and Molecular Diagnosis of Fujian Universities, Xiamen Key Laboratory of Marine and Gene Drugs, School of Medicine, Huaqiao University, Xiamen 361021, China.
Henan Key Laboratory of Chemical Biology and Organic Chemistry, Key Laboratory of Applied Chemistry of Henan Universities, Green Catalysis Center, College of Chemistry, Zhengzhou University, Zhengzhou 450052, China.
Int J Mol Sci. 2021 Mar 18;22(6):3097. doi: 10.3390/ijms22063097.
In this study, detailed information on hepatocellular carcinoma (HCC) cells (HepG-2, SMMC-7721, and HuH-7) and normal human liver cell L02 treated by ferrocene derivatives (compounds , and ) is provided. The cell viability assay showed that compound presented the most potent and selective anti-HCC activity. Further mechanism study indicated that the proliferation inhibition effect of compound was associated with the cycle arrest at the G0/G1 phase and downregulation of cyclin D1/CDK4. Moreover, compound could induce apoptosis in HCC cells by loss of mitochondrial membrane potential (ΔΨm), accumulation of reactive oxygen species (ROS), decrease in Bcl-2, increase in BAX and Bad, translocation of Cytochrome , activation of Caspase-9, -3, and cleavage of PARP. These results indicated that compound would be a promising candidate against HCC through G0/G1 cell cycle arrest-related proliferation inhibition and mitochondrial pathway-dependent apoptosis.
本研究提供了有关肝癌细胞（HepG-2、SMMC-7721 和 HuH-7）和用二茂铁衍生物（化合物 、 和 ）处理的正常人类肝细胞 L02 的详细信息。细胞活力测定表明，化合物 表现出最强和最具选择性的抗肝癌活性。进一步的机制研究表明，化合物 的增殖抑制作用与 G0/G1 期细胞周期阻滞和细胞周期蛋白 D1/CDK4 下调有关。此外，化合物 通过线粒体膜电位（ΔΨm）丧失、活性氧（ROS）积累、Bcl-2 减少、BAX 和 Bad 增加、细胞色素 C 易位、Caspase-9、-3 激活和 PARP 切割诱导 HCC 细胞凋亡。这些结果表明，化合物 通过 G0/G1 细胞周期阻滞相关的增殖抑制和线粒体途径依赖性凋亡，可能成为一种有前途的肝癌治疗候选药物。
