| External factors: | Nutlin-3a |
| Aging type: | Accelerate |
| Aging characteristic: |
| Category: | Chemical compounds |
| Phenotype: | Glioblastoma |
| Experiment: | Flow cytometry//SA-β-gal activity assay//Cell morphological analysis |
| Description: | Nutlin-3a effectively arrested cell-cycle progression in U87MG cells 24 hours after treatment, depleting the S-phase compartment (from 21% to 3%) and increasing the G0/G1 (from 63% to 80%) and G2/M (from 12% to 17%) phase compartments.Cell-cycle arrest persisted 96 h after nutlin-3a incubation,suggesting that nutlin-3a might impede cell cycle progression at both the G1/S and G2/M checkpoints in wild-type p53 U87MG cell line.Nutlin-3a-treated glioma cells acquired an enlarged and flat morphology and expressed the senescence-associated SA-βGal after 4 days of nutlin-3a-incubation, which persisted upon removal the drug. |
| Regulatory pathway: | p53//mTOR |
| R-EF-Pathway: | -- |
| Official symbol(s): | TP53//MTOR |
| Pathway experiment: | Flow cytometry//Western blot |
| Pathway description: | T98G mutant-p53 cells showed no significant differences regarding cell cycle profile when comparing controls (DMSO vehicle) to treated cells. In addition, nutlin-3a induced p21 expression, an important mediator of p53- dependent cell cycle arrest, 24 h after incubation, and it persisted 96 hours after treatment.Western blot analysis of S6 phosphorylation protein suggested that mTOR pathway remains Activate after nutlin-3a in glioma cells. Taken together, these results confirm that nutlin-3a induces senescence in U87MG cells and suggest that it might be dependent on mTOR pathway activity. |
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