| Literature DB >> 33608585 |
Francesca Amoroso1,2, Kimberley Glass3, Reema Singh4, Francisco Liberal3,5, Rebecca E Steele3,6, Sarah Maguire3, Rohinton Tarapore7, Joshua E Allen7, Sandra Van Schaeybroeck3, Karl T Butterworth3, Kevin Prise3, Joe M O'Sullivan3,8, Suneil Jain3,8, David J Waugh9, Ian G Mills10,11,12,13.
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.Entities:
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Year: 2021 PMID： 33608585 PMCID： PMC7896060 DOI： 10.1038/s41598-021-83215-y
Source DB: PubMed Journal: Sci Rep ISSN： 2045-2322 Impact factor: 4.379