TH301 Emerges as a Novel Anti-Oncogenic Agent for Human Pancreatic Cancer Cells: The Dispensable Roles of p53, CRY2 and BMAL1 in TH301-Induced CDKN1A/p21CIP1/WAF1 Upregulation
Abstract
:1. Introduction
2. Results
2.1. TH301-Induced Reduction of Cell Viability and Growth of Pancreatic Cancer Cells in a Mutational Signature-Dependent Fashion
2.2. TH301 Causes Cell Cycle Arrest at the G1-Phase and Alters Protein Expression Profiles of Critical Regulators in Pancreatic Cancer Cells: Mutational Load-Dependent Responses
2.3. TH301 Causes a Strong p53-Independent Induction of the CDKN1A/p21 Cell Cycle Inhibitor in Pancreatic Cancer Cell Environments, Following Mutational Load-Specific Patterns
2.4. TH301 Induces Caspase Repertoire-Mediated Apoptosis in Pancreatic Cancer Cell Settings: Mutational Signature-Dependent Responses
2.5. TH301 Upregulates LC3B-II-Depenent Autophagy in Pancreatic Cancer Cells, Following a Mutational Signature-Independent Pattern
2.6. TH301 Potentiates the Cytopathic Effects of Oxaliplatin by Reducing Pancreatic Cancer Cell Viability
2.7. CRY2 and BMAL1 Are Not Required for the TH301-Driven Induction of p21 Cell Cycle Inhibitor in Pancreatic Cancer Cells
3. Discussion
4. Materials and Methods
4.1. Cell Lines and Culture Conditions
4.2. Inhibitors
4.3. MTT Assay
4.4. Cell Cycle Analysis
4.5. RNA Extraction
4.6. RT-qPCR
4.7. Western Blotting
4.8. Plasmids
4.9. Evaluation of BMAL1 Knock-Down Efficiency
4.10. Lentivirus Production
4.11. Lentivirus Transduction
4.12. Genomic DNA Extraction and PCR Amplification
4.13. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Farmakis, D.; Stravopodis, D.J.; Prombona, A. TH301 Emerges as a Novel Anti-Oncogenic Agent for Human Pancreatic Cancer Cells: The Dispensable Roles of p53, CRY2 and BMAL1 in TH301-Induced CDKN1A/p21CIP1/WAF1 Upregulation. Int. J. Mol. Sci. 2025, 26, 178. https://doi.org/10.3390/ijms26010178
Farmakis D, Stravopodis DJ, Prombona A. TH301 Emerges as a Novel Anti-Oncogenic Agent for Human Pancreatic Cancer Cells: The Dispensable Roles of p53, CRY2 and BMAL1 in TH301-Induced CDKN1A/p21CIP1/WAF1 Upregulation. International Journal of Molecular Sciences. 2025; 26(1):178. https://doi.org/10.3390/ijms26010178
Chicago/Turabian StyleFarmakis, Danae, Dimitrios J. Stravopodis, and Anastasia Prombona. 2025. "TH301 Emerges as a Novel Anti-Oncogenic Agent for Human Pancreatic Cancer Cells: The Dispensable Roles of p53, CRY2 and BMAL1 in TH301-Induced CDKN1A/p21CIP1/WAF1 Upregulation" International Journal of Molecular Sciences 26, no. 1: 178. https://doi.org/10.3390/ijms26010178
APA StyleFarmakis, D., Stravopodis, D. J., & Prombona, A. (2025). TH301 Emerges as a Novel Anti-Oncogenic Agent for Human Pancreatic Cancer Cells: The Dispensable Roles of p53, CRY2 and BMAL1 in TH301-Induced CDKN1A/p21CIP1/WAF1 Upregulation. International Journal of Molecular Sciences, 26(1), 178. https://doi.org/10.3390/ijms26010178