| External factors: | Camptothecin |
| Aging type: | Accelerate |
| Aging characteristic: |
| Category: | Chemical compounds |
| Phenotype: | Colorectal cancer |
| Experiment: | SA-β-gal activity assay//Cell morphological analysis |
| Description: | We found enlarged and flattened cell morphology and increased time-dependent SA-β-gal activity . This suggests that the CRC cells acquire properties of senescence upon CPT treatment. |
| Regulatory pathway: | DDR//AMPK-TSC2-mTOR//ATM-Chk2-p53-p21 |
| R-EF-Pathway: | Activation//--//Activation |
| Official symbol(s): | DDR1//AMPK-TSC2-MTOR//ATM-CHK2-TP53-CDKN1A |
| Pathway experiment: | Immunofluorescence//Western blot |
| Pathway description: | To investigate the activation of DNA damage signaling pathway by low-dose CPT, several key proteins of DDR were detected by immunofluorescence staining and Western blotting. In our study, the expression of γ-H2AX was increased over time as a result of CPT. Low-dose CPT up-regulated the phosphorylation of AMPK and TSC2 while down-regulated the phosphorylation of mTOR over time . Both p53 and p21 increased in a time-dependent manner with low-dose CPT treatment, and the protein levels decreased after the combination treatment of CPT with ATM inhibitor KU55933.Thus, it is possible that CPT induces premature senescence through ATM activation of the Chk2-p53-p21 pathway in HCT116 and RKO cells. |
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