Dieckol induces cell cycle arrest by down-regulating CDK2/cyclin E in response to p21/p53 activation in human tracheal fibroblasts.
Seong-Yeong HeoMin-Seon JeongHyoung Shin LeeWon Sun ParkIl-Whan ChoiMyunggi YiWon-Kyo JungPublished in: Cell biochemistry and function (2021)
The phlorotannin derivative dieckol isolated from Ecklonia cava has been shown to exhibit anti-inflammatory, anti-bacterial, anti-oxidative anti-adipogenic and anti-stenosis activity. However, the role of dieckol in cyclin-dependent kinase 2 (CDK2)/cyclin E signalling, which regulates fibrosis development, has not yet been determined. In this study, we report that dieckol-suppressed cell proliferation through the cell cycle arrest of Hs680.Tr human tracheal fibroblasts. Following consecutive purification, dieckol was identified as a potent bioactive compound. The results showed that dieckol had significant anti-proliferative activity against Hs680.Tr human tracheal fibroblastsWestern blotting analysis also found that dieckol dose-dependently induced the cell cycle arrest of Hs680.Tr fibroblasts in the G0/G1 phase, accompanied by the downregulation of CDK2 and cyclin E and the upregulation of p21 and p53. As attested by molecular docking study, the dieckol interacted with the core interface residues in transforming growth factor-β receptor with high affinity. These findings suggest that dieckol from E. cava inhibits the cell proliferation of Hs680.Tr, potentially through p21- and p53-mediated G0/G1 cell cycle arrest.
Keyphrases
- cell cycle arrest
- pi k akt
- cell death
- cell proliferation
- cell cycle
- signaling pathway
- endothelial cells
- molecular docking
- transforming growth factor
- induced pluripotent stem cells
- epithelial mesenchymal transition
- anti inflammatory
- pluripotent stem cells
- extracellular matrix
- molecular dynamics simulations
- long non coding rna
- diabetic rats
- water soluble
- stress induced
- protein kinase
- recombinant human