| External factors: | Etoposide |
| Aging type: | Accelerate |
| Aging characteristic: |
| Category: | Chemical compounds |
| Phenotype: | Aging |
| Experiment: | SA-β-gal activity assay |
| Description: | After treatment of HepG2 cells with a relatively lower dose of etoposide (10μM), we observed the cells showing the senescence-like growth arrest. When the cells were treated with the low dose of etoposide (10 μM), the activity of senescence-associated β-galactosidase (SA-β-Gal), a well-known late senescence marker, gradually increased in a time-dependent manner. |
| Target gene: | DDR//P53//PRODH//DAO |
| R-EF-Target gene: | --//--//--//-- |
| Official symbol(s): | DDR1//P53//PRODH//DAO |
| Target gene experiment: | Western blot//SA-β-gal activity assay//BrdU assay//CHIP |
| Target gene description: | Consistently, inhibition or depletion of DDR components (ATM, ATR, or Chk1) effectively prevented etoposide-induced senescence. The phosphorylation levels of p53 at Ser20 dramatically increased until 24 h after treatment with the low dose of etoposide accompanying the increase of p53 protein, and sustained for up to 48h, which is consistent with the prolonged activation of Chk1. Knockdown of p53 remarkably decreased etoposide-induced senescence as determined by SA-β-Gal staining and 5-Bromo-2 -deoxyuridine (BrdU) incorporation assay, suggesting that senescence induced by the low dose of etoposide is highly dependent on p53.Chromatin immunoprecipitation (ChIP) assay using the anti-p53 antibody in HepG2 cells revealed that p53 bound to the genomic regions of PRODH and DAO when treated with etoposide. |
| Regulatory pathway: | -- |
| R-EF-Pathway: | -- |
| Pathway experiment: | -- |
| Pathway description: | -- |
Annotation: