| External factors: | TMZ |
| Aging type: | Accelerate |
| Aging characteristic: |
| Category: | Chemical compounds |
| Phenotype: | Glioblastoma |
| Experiment: | Flow cytometry//PI staining//SA-β-gal activity assay |
| Description: | The data revealed that repeated low-dose TMZ exposure is highly efficient in inducing senescence in p53 proficient U87 (up to 60%) and LN229 (up to 80%) cells .Compared to the high level of senescence, apoptosis and necrosis were induced at low levels (up to 20%) upon repeated treatment of U87 and up to 10% necrosis and 25% apoptosis upon single exposure. Also in LN229 cells repeated treatment induced up to 20% apoptosis and necrosis and single exposure induced up to 15% apoptosis and necrosis . |
| Target gene: | P21//NF-κB |
| R-EF-Target gene: | --//-- |
| Official symbol(s): | P21//NFKB1 |
| Target gene experiment: | SA-β-gal activity assay//Flow cytometry |
| Target gene description: | In line with this, knockdown of p21 completely abrogated the induction of senescence , The results showed a dramatic reduction in temozolomide-induced senescence following NF-κB inhibition . |
| Regulatory pathway: | MRN-ATR |
| R-EF-Pathway: | -- |
| Official symbol(s): | ATR |
| Pathway experiment: | SA-β-gal activity assay |
| Pathway description: | To analyze whether this is also true for the activation of senescence, the DDR factors ATM, ATR, MRN, and DNA-PKcs were pharmacologically inhibited and the frequency of senescence was measured in LN229 cells (proficient for p53 and deficient for MGMT) by scoring senescence-associated β-galactosidase (β-Gal)–positive cells. To identify the senescence-inducing DNA lesions, activation of senescence was also measured in LN229 cells that express MGMT following transfection with MGMT cDNA (LN229-MGMT). The data show that senescence was induced only in MGMT-deficient LN229 glioma cells, but not in the MGMT-proficient LN229-MGMT isogenic cell line. |
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