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Modulating the unfolded protein response with ONC201 to impact on radiation response in prostate cancer cells
- Source :
- Scientific Reports, Amoroso, F, Glass, K, Singh, R, Liberal, F, Steele, R E, Maguire, S, Tarapore, R, Allen, J E, Van Schaeybroeck, S, Butterworth, K T, Prise, K, O'Sullivan, J M, Jain, S, Waugh, D J & Mills, I G 2021, ' Modulating the unfolded protein response with ONC201 to impact on radiation response in prostate cancer cells ', Scientific Reports, vol. 11, no. 1, pp. 4252 . https://doi.org/10.1038/s41598-021-83215-y, Scientific Reports, Vol 11, Iss 1, Pp 1-16 (2021)
- Publication Year :
- 2021
- Publisher :
- Nature, 2021.
-
Abstract
- Prostate cancer (PCa) is the most common non-cutaneous cancer in men and a notable cause of cancer mortality when it metastasises. The unfolded protein response (UPR) can be cytoprotective but when acutely activated can lead to cell death. In this study, we sought to enhance the acute activation of the UPR using radiation and ONC201, an UPR activator. Treating PCa cells with ONC201 quickly increased the expression of all the key regulators of the UPR and reduced the oxidative phosphorylation, with cell death occurring 72 h later. We exploited this time lag to sensitize prostate cancer cells to radiation through short-term treatment with ONC201. To understand how priming occurred, we performed RNA-Seq analysis and found that ONC201 suppressed the expression of cell cycle and DNA repair factors. In conclusion, we have shown that ONC201 can prime enhanced radiation response.
- Subjects :
- Male
Programmed cell death
DNA Repair
DNA repair
Cell Survival
Pyridines
Science
Priming (immunology)
Antineoplastic Agents
Urological cancer
Radiation Tolerance
Article
Prostate cancer
SDG 3 - Good Health and Well-being
Cell Line, Tumor
medicine
Humans
unfolded protein response (UPR)
Prostate cancer (PCa)
Cancer
Multidisciplinary
Cell Death
business.industry
Activator (genetics)
Cell Cycle
fungi
Imidazoles
Prostatic Neoplasms
Cell cycle
medicine.disease
Mitochondria
Gene Expression Regulation, Neoplastic
Pyrimidines
Oncology
Unfolded protein response
Cancer research
cancer cells
Unfolded Protein Response
Medicine
business
Signal Transduction
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Scientific Reports, Amoroso, F, Glass, K, Singh, R, Liberal, F, Steele, R E, Maguire, S, Tarapore, R, Allen, J E, Van Schaeybroeck, S, Butterworth, K T, Prise, K, O'Sullivan, J M, Jain, S, Waugh, D J & Mills, I G 2021, ' Modulating the unfolded protein response with ONC201 to impact on radiation response in prostate cancer cells ', Scientific Reports, vol. 11, no. 1, pp. 4252 . https://doi.org/10.1038/s41598-021-83215-y, Scientific Reports, Vol 11, Iss 1, Pp 1-16 (2021)
- Accession number :
- edsair.doi.dedup.....5f8ce160b35ed9eb414fc47c362ede7e