Effects of cisplatin-5-fluorouracil combination therapy on oxidative stress, DNA damage, mitochondrial apoptosis, and death receptor signalling in retinal pigment epithelium cells

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dc.authoridDoganlar, Zeynep Banu/0000-0002-1365-9897
dc.authoridDOĞAN, AYTEN/0000-0003-2525-785X
dc.authoridGüçlü, Hande/0000-0002-3021-0493
dc.authoridDoganlar, Oguzhan/0000-0003-2654-7269
dc.authorwosidDoğanlar, Oğuzhan/A-2315-2019
dc.authorwosidDoganlar, Zeynep Banu/B-4845-2008
dc.authorwosidDOĞAN, AYTEN/ABA-6754-2020
dc.authorwosidGüçlü, Hande/AAW-9756-2020
dc.authorwosidOzal, Sadık Altan/B-5123-2019
dc.contributor.authorGuclu, Hande
dc.contributor.authorDoganlar, Zeynep Banu
dc.contributor.authorGurlu, Vuslat Pelitli
dc.contributor.authorOzal, Altan
dc.contributor.authorDogan, Ayten
dc.contributor.authorTurhan, Meryem Aysenur
dc.contributor.authorDoganlar, Oguzhan
dc.date.accessioned2024-06-12T10:56:34Z
dc.date.available2024-06-12T10:56:34Z
dc.date.issued2018
dc.departmentTrakya Üniversitesien_US
dc.description.abstractAim: Combination therapies of cisplatin with 5-FU (PF) are an effective solution and have been widely used for the treatment of various categories of cancer including anal, gastrointestinal, and oral cancer, as well as head and neck tumors. The effects of combined PF treatment on vital intracellular signalling pathways in nontargeted cells remain unclear. The aim of this study is to explain the possible mechanisms by which combined PF treatment results in retinal toxicity and to investigate the effects of PF on important vital signalling pathways in ARPE 19 retinal pigmented epithelial cells.Materials and methods: We analysed the cellular and molecular effects of PF on cell viability, oxidative stress, gene repair response, and induction of apoptosis in ARPE 19 cells using molecular probe fluorescent staining, cell cytometer, RAPD, qRT-PCR, and western blot assays.Results: We determined that PF causes excessive generation of reactive oxygen species (ROS) and prevents ROS scavenging by suppressing antioxidant systems. We found induction of DNA damage, particularly mismatch and double strand break repair, in ARPE 19 cells treated with PF. In this study, PF also induced both the intrinsic apoptosis pathway and death receptor signalling in ARPE 19 cells.Conclusions: Our data proved that PF causes cytotoxicity and genotoxicity, at both the cellular and molecular levels, in ARPE 19 cells following particularly prolonged treatment (48h). Additionally, our results suggest key molecular signals for prevention strategies that can be developed to reduce the severe side effects of PF chemotherapy.en_US
dc.identifier.doi10.1080/15569527.2018.1456548
dc.identifier.endpage304en_US
dc.identifier.issn1556-9527
dc.identifier.issn1556-9535
dc.identifier.issue3en_US
dc.identifier.pmid29606027en_US
dc.identifier.scopus2-s2.0-85045745619en_US
dc.identifier.scopusqualityQ3en_US
dc.identifier.startpage291en_US
dc.identifier.urihttps://doi.org/10.1080/15569527.2018.1456548
dc.identifier.urihttps://hdl.handle.net/20.500.14551/19840
dc.identifier.volume37en_US
dc.identifier.wosWOS:000438110100014en_US
dc.identifier.wosqualityQ4en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherTaylor & Francis Ltden_US
dc.relation.ispartofCutaneous And Ocular Toxicologyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectCisplatinen_US
dc.subject5-Fluorouracilen_US
dc.subjectPF Armen_US
dc.subjectCytotoxicityen_US
dc.subjectGenotoxicityen_US
dc.subjectDNA Damageen_US
dc.subjectOxidative Stressen_US
dc.subjectApoptosisen_US
dc.subjectARPE 19en_US
dc.subjectLeft Homonymous Hemianopiaen_US
dc.subjectHeat-Shock Proteinsen_US
dc.subjectTesticular-Carcinomaen_US
dc.subjectOcular Complicationsen_US
dc.subjectCancer-Chemotherapyen_US
dc.subjectCisplatinen_US
dc.subjectToxicityen_US
dc.subject5-Fluorouracilen_US
dc.subjectP21en_US
dc.subjectExpressionen_US
dc.titleEffects of cisplatin-5-fluorouracil combination therapy on oxidative stress, DNA damage, mitochondrial apoptosis, and death receptor signalling in retinal pigment epithelium cellsen_US
dc.typeArticleen_US

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