The response of human ectomesenchymal dental pulp stem cells to cisplatin treatment
Language English Country Great Britain, England Media print-electronic
Document type Comparative Study, Journal Article, Research Support, Non-U.S. Gov't
- MeSH
- Enzyme Activation drug effects MeSH
- Apoptosis drug effects MeSH
- Cell Culture Techniques MeSH
- Cell Cycle drug effects MeSH
- Cisplatin toxicity MeSH
- Cytostatic Agents toxicity MeSH
- Ectoderm cytology drug effects MeSH
- Extracellular Signal-Regulated MAP Kinases drug effects MeSH
- Fibroblasts drug effects MeSH
- Phosphorylation MeSH
- Cyclin-Dependent Kinase Inhibitor p21 drug effects MeSH
- Protein Kinase Inhibitors pharmacology MeSH
- JNK Mitogen-Activated Protein Kinases drug effects MeSH
- Caspase 3 drug effects MeSH
- Caspase 7 drug effects MeSH
- Caspase 8 drug effects MeSH
- Caspase 9 drug effects MeSH
- Skin cytology drug effects MeSH
- Humans MeSH
- MAP Kinase Signaling System drug effects MeSH
- Mesenchymal Stem Cells drug effects MeSH
- p38 Mitogen-Activated Protein Kinases drug effects MeSH
- Mutagens toxicity MeSH
- Tumor Suppressor Protein p53 drug effects MeSH
- Cell Proliferation drug effects MeSH
- Serine drug effects MeSH
- Cell Survival drug effects MeSH
- Dental Pulp cytology drug effects MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Comparative Study MeSH
- Names of Substances
- CASP8 protein, human MeSH Browser
- CDKN1A protein, human MeSH Browser
- Cisplatin MeSH
- Cytostatic Agents MeSH
- Extracellular Signal-Regulated MAP Kinases MeSH
- Cyclin-Dependent Kinase Inhibitor p21 MeSH
- Protein Kinase Inhibitors MeSH
- JNK Mitogen-Activated Protein Kinases MeSH
- Caspase 3 MeSH
- Caspase 7 MeSH
- Caspase 8 MeSH
- Caspase 9 MeSH
- p38 Mitogen-Activated Protein Kinases MeSH
- Mutagens MeSH
- Tumor Suppressor Protein p53 MeSH
- Serine MeSH
AIM: To determine the response of dental pulp stem cells (DPSCs) to DNA-damaging cytostatic cisplatin and compare it with the response of normal human dermal fibroblasts (HDFs). METHODOLOGY: Dental pulp stem cells were exposed to 5, 10, 20 or 40 μmol L(-1) of cisplatin. The proliferation of affected cells was assessed by a Z2 Counter and viability was assessed by means of a Vi-Cell XR using Trypan blue exclusion staining. Cell cycle analysis and induction of apoptosis were performed by flow cytometry. Induction of apoptosis was determined by monitoring the activities of caspases. The expression of proteins was detected by electrophoresis and Western blotting. The descriptive statistics of the results was analyzed by Student's t-test. RESULTS: Dental pulp stem cells had a greater genotoxic stress response to cisplatin compared to HDFs. All three main Mitogen-activated protein kinases (MAPK) families - extracellular signal-regulated kinases (ERK), c-Jun-N-terminal kinase (JNK) and p38 were activated after treatment of DPSCs with cisplatin. The activation of MAPK pathways was not observed in HDFs exposed to cisplatin. The exposure of DPSCs and HDFs to cisplatin provoked an increase in p53 and p21 expression and p53 phosphorylation of serine 15. Higher concentrations of cisplatin reduced the viability of DPSCs and HDFs and induced the activation of caspases 3/7 and 9. CONCLUSION: Dental pulp stem cells had a greater genotoxic stress response to cisplatin compared to HDFs. Cisplatin in higher concentrations triggered activation of MAPK and apoptosis in DPSCs but not in HDFs.
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