Biochemical and proteomic analysis of a potential anticancer agent: Palladium(II) saccharinate complex of terpyridine acting through double strand break formation

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dc.authorid0000-0002-8814-7351
dc.contributor.authorAdıgüzel, Zelal
dc.contributor.authorBaykal, Ahmet Tarık
dc.contributor.authorKaçar, Ömer
dc.contributor.authorYılmaz, Veysel Turan
dc.contributor.authorUlukaya, Engin
dc.contributor.authorAçılan, Ceyda
dc.date.accessioned10.07.201910:49:13
dc.date.accessioned2019-07-10T20:01:29Z
dc.date.available10.07.201910:49:13
dc.date.available2019-07-10T20:01:29Z
dc.date.issued2014
dc.departmentİstanbul Medipol Üniversitesi, Tıp Fakültesi, Temel Tıp Bilimleri Bölümü, Tıbbi Biyokimya Ana Bilim Dalı
dc.descriptionWOS: 000344636500065
dc.descriptionPubMed ID: 25210790
dc.description.abstractMetal based chemotherapeutic drugs are widely used as an effective method to defeat various cancers. In this study, the mechanism of action of a novel therapeutic agent, [Pd(sac)(terpy)](sac)center dot 4H(2)O (sac = saccharinate, and terpy = 2,2':6',2 ''-terpyridine) was studied. To better understand the proteomic changes in response to this agent, we performed nano LC-MS/MS analyses in human breast cancer cells (MDA-MB-231). Thirty proteins were identified to be differentially expressed more than 40% after drug treatment. Many cellular pathways were affected, including proteins involved in DNA repair, apoptosis, energy metabolism, protein folding, cytoskeleton, pre-mRNA maturation, or protein translation. The changes in protein expression were further verified for XRCC5, which plays a role in double strand break (DSB) repair, and ubiquitin, which is involved in protein degradation and apoptosis. The elevated XRCC5 levels were suggestive of increased DSBs. The presence of DSBs was confirmed by smearing of plasmid DNA in vitro and induction of gamma H2AX foci in vivo. There was also increased intracellular reactive oxygen species (ROS) formation, as detected by 2',7'-dichlorofluorescein diacetate (DCFDA) staining. Scavenging ROS by N-acetylcysteine rescued cell death in response to Pd(II) treatment, potentially explaining how the Pd(II) complex damaged the DNA. The details of this analysis and the significance will be discussed during the scope of this work.
dc.identifier.citationAdıgüzel, Z., Baykal, A. T., Kaçar, Ö., Yılmaz, V. T., Ulukaya, E. ve Açılan, C. (2014). Biochemical and proteomic analysis of a potential anticancer agent: Palladium(II) saccharinate complex of terpyridine acting through double strand break formation. Journal of Proteome Research, 13(11), 5240-5249. https://dx.doi.org/10.1021/pr5006718
dc.identifier.doi10.1021/pr5006718
dc.identifier.endpage5249
dc.identifier.issn1535-3893
dc.identifier.issn1535-3907
dc.identifier.issue11
dc.identifier.scopusqualityQ1
dc.identifier.startpage5240
dc.identifier.urihttps://dx.doi.org/10.1021/pr5006718
dc.identifier.urihttps://hdl.handle.net/20.500.12511/3299
dc.identifier.volume13
dc.identifier.wosqualityQ1
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherAmerican Chemical Society
dc.relation.ispartofJournal of Proteome Researchen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.subjectPalladium(II) Saccharinate Complex With Terpyridine
dc.subjectAnticancer Drugs
dc.subjectDNA Double Strand Breaks
dc.subjectReactive Oxygen Species
dc.subjectNonhomologous End Joining
dc.subjectApoptosis
dc.subjectProteomics
dc.titleBiochemical and proteomic analysis of a potential anticancer agent: Palladium(II) saccharinate complex of terpyridine acting through double strand break formation
dc.typeArticle

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