External factors
| External factors: |
Mithramycin |
| Category: |
Chemical compounds |
| Phenotype: |
Malignant pleural mesothelioma |
| Experimental category: |
HL |
| Experiment: |
MTS assay//SA-β-gal activity assay//Flow cytometry |
| Description: |
MTS assays demonstrated that 24-hour mithramycin exposure dramatically inhibited proliferation of MES1 and MES7 cells.Mithramycin significantly diminished growth of subcutaneous MES1 and MES7 xenografts in a dose-dependent manner. Flow cytometric experiments demonstrated dose-dependent accumulation of MPM cells in G0–G1without a sub-G0 fraction consistent with a G0–G1arrest immediately following 24-hour mithramycin exposure. Histochemical experiments performed at this time point demonstrated that mithramycin mediated dose-dependent increases in β-galactosidase expression indicative of senescence in MPM cells. |
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Regulatory relationship
| R-EF-Target gene:
|
Downregulation// |
| Official symbol(s): |
SP1//P53 |
| Target gene experiment: |
qRT-PCR//Western blot |
| Target gene description: |
qRT-PCR and immunoblot experiments demonstrated dose-dependent decreases in SP1 expression in both cell lines following mithramycin exposure.In addition, mithramycin mediated dose-dependent increases in p53, p21, PMAIP1, and PRDM1 in vitro and in vivo . Subsequent immunoblot experiments confirmed results of qRT-PCR experiments.Immunoblot experiments demonstrated dose-dependent increases in gH2AX in MES1 and MES7 cells indicative of DNA damage, which coincided with increases in total p53 as well as acetylated p53-K320, K373, K382, and phosphorylated p53-S15 levels in MES7 cells, and to a lesser extent, MES1 cells following mithramycin exposure . |
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Aging network
Annotation:
The green line represents Upregulation.
The purple line represents Downregulation.
The orange line represents Activation.
The yellow line represents Inhibition.
The gray line represents Unclear.
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