Novel Ferrocene Derivatives Induce G0/G1 Cell Cycle Arrest and Apoptosis through the Mitochondrial Pathway in Human Hepatocellular Carcinoma.
Jianrong ZhengLiao ZengMingqing TangHongjun LinChao PiRuian XuXiuling CuiPublished in: International journal of molecular sciences (2021)
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 1, 2 and 3) is provided. The cell viability assay showed that compound 1 presented the most potent and selective anti-HCC activity. Further mechanism study indicated that the proliferation inhibition effect of compound 1 was associated with the cycle arrest at the G0/G1 phase and downregulation of cyclin D1/CDK4. Moreover, compound 1 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 c, activation of Caspase-9, -3, and cleavage of PARP. These results indicated that compound 1 would be a promising candidate against HCC through G0/G1 cell cycle arrest-related proliferation inhibition and mitochondrial pathway-dependent apoptosis.
Keyphrases
- cell cycle arrest
- cell death
- pi k akt
- signaling pathway
- reactive oxygen species
- oxidative stress
- induced apoptosis
- dna damage
- cell proliferation
- cell cycle
- endothelial cells
- mesenchymal stem cells
- healthcare
- single cell
- high throughput
- dna repair
- climate change
- social media
- cell therapy
- risk assessment
- dna binding
- transcription factor
- human health
- anti inflammatory