A trans-platinum(II) complex induces apoptosis in cancer stem cells of breast cancer

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dc.authoridEngin Ulukaya / 0000-0003-4875-5472en_US
dc.authorscopusidEngin Ulukaya / 6602927353
dc.authorwosidEngin Ulukaya / K-5792-2018
dc.contributor.authorAztopal, Nazlıhan
dc.contributor.authorKarakaş, Didem
dc.contributor.authorCevatemre, Buse
dc.contributor.authorArı, Ferda
dc.contributor.authorİçsel, Ceyda
dc.contributor.authorDaidone, Maria G.
dc.contributor.authorUlukaya, Engin
dc.date.accessioned2020-08-30T20:08:20Z
dc.date.available2020-08-30T20:08:20Z
dc.date.issued2017
dc.departmentİstinye Üniversitesi, Tıp Fakültesi, Temel Tıp Bilimleri Bölümüen_US
dc.description.abstractRecent accumulating evidence has supported the notion that tumors have hierarchically organized heterogeneous cell populations and a small subpopulation of cells, termed cancer stem cells (CSCs), are responsible for tumor initiation, maintenance as well as drug resistance. Therefore, targeting the CSCs along with the other cancer cells has been the most important topic during the last decade. In the present study, we evaluated the cytotoxic activity of trans-[PtCl2(2-hepy) 2] [2-hepy = 2-(2-hydroxyethyl) pyridine] complex and the mechanism of cell death in breast CSCs. Stemness markers, Oct-4 and Sox2, were determined in mammospheres by western blotting. Cytotoxicity was assessed using the ATP viability assay. Cell death was fluorescently visualized and further confirmed by flow cytometry as well as gene expression analysis. The Pt(II) complex significantly reduced the cell viability, prevented mammosphere formation and disrupted mammosphere structures in a dose-dependent manner (0100 lM). The mode of cell death was apoptosis and it was shown by the presence of caspase 3/7 activity, Annexin V-FITC positivity, decreased mitochondrial membrane potential and increased expressions of pro-apoptotic genes (TNFRSF10A and HRK). Interestingly, necroptosis was also observed by the evidence of increased MLKL expression. In conclusion, the Pt(II) complex seems to be a highly promising anticancer compound due to its promising cytotoxic activity on CSCs. Therefore, it deserves in vivo further studies for the proof-of-concept. (C) 2016 Elsevier Ltd. All rights reserved.en_US
dc.description.sponsorshipTUBITAK (The Scientific and Technological Research Council of Turkey)Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [112T726]en_US
dc.description.sponsorshipThis work was supported by the Research Fund of TUBITAK (The Scientific and Technological Research Council of Turkey) for the project that is numbered 112T726. The authors are grateful to Dr. Veysel T. Yilmaz (Uludag University, Turkey) for providing us the Pt(II) complex and Dr. Raffaella Villa (Fondazione IRCCS Istituto Nazionale dei Tumori, Italy) for the interpretation the data.en_US
dc.identifier.citationAztopal, N., Karakas, D., Cevatemre, B., Ari, F., Icsel, C., Daidone, M. G., & Ulukaya, E. (2017). A trans-platinum(II) complex induces apoptosis in cancer stem cells of breast cancer. Bioorganic and Medicinal Chemistry, 25(1), 269–276. https://doi.org/10.1016/j.bmc.2016.10.032en_US
dc.identifier.doi10.1016/j.bmc.2016.10.032en_US
dc.identifier.endpage276en_US
dc.identifier.issn0968-0896en_US
dc.identifier.issn1464-3391en_US
dc.identifier.issue1en_US
dc.identifier.pmid27839660en_US
dc.identifier.scopus2-s2.0-85006272143en_US
dc.identifier.scopusqualityQ2en_US
dc.identifier.startpage269en_US
dc.identifier.urihttps://doi.org/10.1016/j.bmc.2016.10.032
dc.identifier.urihttps://hdl.handle.net/20.500.12713/923
dc.identifier.volume25en_US
dc.identifier.wosWOS:000397052800029en_US
dc.identifier.wosqualityQ2en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.institutionauthorUlukaya, Enginen_US
dc.language.isoenen_US
dc.publisherPergamon-Elsevier Science Ltden_US
dc.relation.ispartofBioorganic & Medicinal Chemistryen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectAnti-Growth Effecten_US
dc.subjectApoptosisen_US
dc.subjectBreast Cancer Stem Cellsen_US
dc.subjectNecroptosisen_US
dc.subjectPlatinumen_US
dc.titleA trans-platinum(II) complex induces apoptosis in cancer stem cells of breast canceren_US
dc.typeArticleen_US

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