Publication: The suppression of atr/chk1 pathway by elimusertib atr inhibitor in triple negative breast cancer cells
dc.contributor.author | Eskiler, Gamze Guney | |
dc.contributor.buuauthor | Hacıefendi, Ayten | |
dc.contributor.department | Tıp Fakültesi | |
dc.contributor.department | Tıbbi Biyoloji Ana Bilim Dalı | |
dc.contributor.orcid | 0000-0002-2088-9914 | |
dc.contributor.researcherid | AAB-6011-2022 | |
dc.date.accessioned | 2024-10-31T06:10:11Z | |
dc.date.available | 2024-10-31T06:10:11Z | |
dc.date.issued | 2023-01-01 | |
dc.description.abstract | Objectives: Genomic instability in cancer cells is based on the aberrant activation of deoxyribonucleic acid (DNA) damage response and repair mechanisms. Targeting Ataxia telangiectasia and Rad3-related (ATR) inhibition in cancer treatment have attracted attention in recent years. In the current study, we aimed for the first time to determine the anti-cancer effects of Elimusertib, an ATR inhibitor, on triple negative breast cancer (TNBC). Methods: The cytotoxic and apoptotic effects of Elimusertib were analyzed by Water-Soluble Tetrazolium 1 (WST-1), Annexin V, cell cycle and acridine orange/propidium iodide staining. Furthermore, Elimusertib induced mitochondrial damage and the intracellular reactive oxygen species were evaluated. Additionally, the inhibition of ATR-Checkpoint kinase 1 (Chk1) DNA damage response and the induction of apoptotic death was analyzed by western blot analysis. Results: Our preliminary findings revealed that Elimusertib significantly decreased the viability of MDA-MB-231 TNBC cells with toxicity in MCF-10A cells (P<0.05). Elimusertib caused apoptotic death through gap phase (G0)/growth 1 phase (G1) accumulation, caspase-3 activity and mitochondrial damage. Additionally, Elimusertib significantly suppressed the ATR-based DNA damage response and mediated cell cycle checkpoint. Conclusions: Our findings suggest that Elimusertib suppresses the ATR-based Chk1 pathway in TNBC cells. Therefore, ATR inhibition by Elimusertib could be a potential therapeutic strategy especially in tumor protein p53 (p53) mutant TNBC patients. | |
dc.description.sponsorship | Sakarya Üniversitesi 2022-7-24-28 | |
dc.identifier.endpage | 4911 | |
dc.identifier.issn | 1943-8141 | |
dc.identifier.issue | 7 | |
dc.identifier.startpage | 4902 | |
dc.identifier.uri | https://hdl.handle.net/11452/47235 | |
dc.identifier.volume | 15 | |
dc.identifier.wos | 001048895000004 | |
dc.indexed.wos | WOS.SCI | |
dc.language.iso | en | |
dc.publisher | E-century Publishing Corp | |
dc.relation.journal | American Journal Of Translational Research | |
dc.subject | Target | |
dc.subject | P53 | |
dc.subject | Dna damage response | |
dc.subject | Atr | |
dc.subject | Cell cycle | |
dc.subject | Apoptosis | |
dc.subject | Triple negative breast cancer | |
dc.subject | Science & technology | |
dc.subject | Life sciences & biomedicine | |
dc.subject | Oncology | |
dc.subject | Medicine, research & experimental | |
dc.subject | Oncology | |
dc.subject | Research & experimental medicine | |
dc.title | The suppression of atr/chk1 pathway by elimusertib atr inhibitor in triple negative breast cancer cells | |
dc.type | Article | |
dspace.entity.type | Publication | |
local.contributor.department | Tıp Fakültesi/Tıbbi Biyoloji Ana Bilim Dalı |