Novel Anthraquinone Compounds Inhibit Colon Cancer Cell Proliferation via the Reactive Oxygen Species/JNK Pathway.
Yuying LiFang GuoYingying GuanTing-Gui ChenKaiqing MaLi-Wei ZhangZhuanhua WangQiang SuLiheng FengYaoming LiuYuzhi ZhouPublished in: Molecules (Basel, Switzerland) (2020)
A series of amide anthraquinone derivatives, an important component of some traditional Chinese medicines, were structurally modified and the resulting antitumor activities were evaluated. The compounds showed potent anti-proliferative activities against eight human cancer cell lines, with no noticeable cytotoxicity towards normal cells. Among the candidate compounds, 1-nitro-2-acyl anthraquinone-leucine (8a) showed the greatest inhibition of HCT116 cell activity with an IC50 of 17.80 μg/mL. In addition, a correlation model was established in a three-dimensional quantitative structure-activity relationship (3D-QSAR) study using Comparative Molecular Field Analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA). Moreover, compound 8a effectively killed tumor cells by reactive oxygen species (ROS)-JNK activation, causing an increase in ROS levels, JNK phosphorylation, and mitochondrial stress. Cytochrome c was then released into cytoplasm, which, in turn activated the cysteine protease pathway and ultimately induced tumor cell apoptosis, suggesting a potential use of this compound for colon cancer treatment.
Keyphrases
- reactive oxygen species
- induced apoptosis
- cell death
- structure activity relationship
- cell proliferation
- cell cycle arrest
- signaling pathway
- dna damage
- endoplasmic reticulum stress
- endothelial cells
- single cell
- molecular dynamics
- papillary thyroid
- cell cycle
- pi k akt
- diabetic rats
- living cells
- climate change
- stem cells
- mesenchymal stem cells
- fatty acid
- young adults
- protein kinase
- squamous cell