Publication:
The suppression of atr/chk1 pathway by elimusertib atr inhibitor in triple negative breast cancer cells

dc.contributor.authorEskiler, Gamze Guney
dc.contributor.buuauthorHacıefendi, Ayten
dc.contributor.departmentTıp Fakültesi
dc.contributor.departmentTıbbi Biyoloji Ana Bilim Dalı
dc.contributor.orcid0000-0002-2088-9914
dc.contributor.researcheridAAB-6011-2022
dc.date.accessioned2024-10-31T06:10:11Z
dc.date.available2024-10-31T06:10:11Z
dc.date.issued2023-01-01
dc.description.abstractObjectives: 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.sponsorshipSakarya Üniversitesi 2022-7-24-28
dc.identifier.endpage4911
dc.identifier.issn1943-8141
dc.identifier.issue7
dc.identifier.startpage4902
dc.identifier.urihttps://hdl.handle.net/11452/47235
dc.identifier.volume15
dc.identifier.wos001048895000004
dc.indexed.wosWOS.SCI
dc.language.isoen
dc.publisherE-century Publishing Corp
dc.relation.journalAmerican Journal Of Translational Research
dc.subjectTarget
dc.subjectP53
dc.subjectDna damage response
dc.subjectAtr
dc.subjectCell cycle
dc.subjectApoptosis
dc.subjectTriple negative breast cancer
dc.subjectScience & technology
dc.subjectLife sciences & biomedicine
dc.subjectOncology
dc.subjectMedicine, research & experimental
dc.subjectOncology
dc.subjectResearch & experimental medicine
dc.titleThe suppression of atr/chk1 pathway by elimusertib atr inhibitor in triple negative breast cancer cells
dc.typeArticle
dspace.entity.typePublication
local.contributor.departmentTıp Fakültesi/Tıbbi Biyoloji Ana Bilim Dalı

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