c-Myc Sustains Pancreatic Cancer Cell Survival and mutp53 Stability through the Mevalonate Pathway
Abstract
:1. Introduction
2. Materials and Methods
2.1. Cell Cultures and Treatments
2.2. Trypan Blue Assay
2.3. c-Myc Silencing
2.4. Western Blot Analysis
2.5. Antibodies
2.6. Densitometric Analysis
2.7. Measurement of Intracellular Reactive Oxygen Species (ROS)
2.8. Clonogenic Assay
2.9. Statistical Analysis
3. Results
3.1. Pharmacological or Genetic Inhibition of c-Myc Impairs Pancreatic Cell Survival in Correlation with mutp53 Downregulation
3.2. c-Myc Inhibition Promotes the Proteasomal Degradation of mutp53 Independently of HSP Modulation
3.3. c-Myc Inhibitor Increases DNA Damage in Pancreatic Cancer Cells
3.4. c-Myc Sustains mutp53 Expression Level and Pancreatic Cell Survival through the Mevalonate Pathway
3.5. Mevalonate Supplementation Restored mutp53 Expression and Prevented DNA Damage in Pancreatic Cancer Cells Undergoing c-Myc Inhibition
3.6. Mevalonate Supplementation Rescued Cell Survival and the Inhibition of Colony Formation Induced by c-Myc Inhibition
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Romeo, M.A.; Gilardini Montani, M.S.; Arena, A.; Benedetti, R.; D’Orazi, G.; Cirone, M. c-Myc Sustains Pancreatic Cancer Cell Survival and mutp53 Stability through the Mevalonate Pathway. Biomedicines 2022, 10, 2489. https://doi.org/10.3390/biomedicines10102489
Romeo MA, Gilardini Montani MS, Arena A, Benedetti R, D’Orazi G, Cirone M. c-Myc Sustains Pancreatic Cancer Cell Survival and mutp53 Stability through the Mevalonate Pathway. Biomedicines. 2022; 10(10):2489. https://doi.org/10.3390/biomedicines10102489
Chicago/Turabian StyleRomeo, Maria Anele, Maria Saveria Gilardini Montani, Andrea Arena, Rossella Benedetti, Gabriella D’Orazi, and Mara Cirone. 2022. "c-Myc Sustains Pancreatic Cancer Cell Survival and mutp53 Stability through the Mevalonate Pathway" Biomedicines 10, no. 10: 2489. https://doi.org/10.3390/biomedicines10102489