Browsing by Author "Eskiler, Gamze Guney"

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    The regulatory effect of cabazitaxel on epithelial-mesenchymal transition in metastatic prostate cancer
    (Wolters Kluwer Medknow Publications, 2023-01-01) Eskiler, Gamze Guney; ERYILMAZ, IŞIL EZGİ; EGELİ, ÜNAL; ÇEÇENER, GÜLŞAH; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyoloji Anabilim Dalı.; 0000-0002-2088-9914; AAB-6011-2022
    Introduction:Epithelial-mesenchymal transition (EMT) is a critical mechanism that promotes cancer cells to metastasis. Therefore, EMT regulation has become an important target in anticancer therapy approaches in recent years. However, in metastatic prostate cancer (PC), the EMT regulatory effect has not fully understood for cabazitaxel (Cbx), a third line taxane-based chemotherapeutic for metastatic castration-resistant PC.Aim:In this study, we investigated the antimetastatic and EMT-regulatory effects of Cbx on hormone-sensitive metastatic PC cells.Materials and Methods:The anticancer effects of Cbx were assessed by WST-1 and Annexin V analysis. The antimetastatic effect of Cbx was evaluated by wound healing and quantitative reverse transcription polymerase chain reaction through EMT-mesenchymal-to-epithelial transition (MET) markers as well as EMT-repressor microRNAs (miRNAs) in Cbx-treated LNCaP cells.Results:Our results showed that, in addition to its apoptotic and anti-migratory activities, Cbx exhibited the EMT-repressor effects through the prominent downregulation of matrix metalloproteinase-9 and Snail levels as EMT-promoting factors, and the significant upregulation of the certain miRNAs, including miR-205, miR-524, and miR-124, which play a role in EMT-repressing by targeting regulators of the EMT-associated genes.Conclusion:Although further evaluations are needed to improve the findings, we showed that, in addition to its classical taxane function, Cbx has a regulatory effect on EMT-MET cycling in hormone-sensitive metastatic PC.
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    Publication
    The suppression of atr/chk1 pathway by elimusertib atr inhibitor in triple negative breast cancer cells
    (E-century Publishing Corp, 2023-01-01) Eskiler, Gamze Guney; Hacıefendi, Ayten; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyoloji Anabilim Dalı.; 0000-0002-2088-9914; AAB-6011-2022
    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.