Publication:
Synthesis, biological characterization and evaluation of molecular mechanisms of novel copper complexes as anticancer agents

dc.contributor.authorAçılan, Ceyda
dc.contributor.authorAdıguzel, Zelal
dc.contributor.authorRibeiro, Nádia
dc.contributor.authorCorreia, Isabel
dc.contributor.authorPessoa, João Costa
dc.contributor.buuauthorCevatemre, Buse
dc.contributor.buuauthorKarakaş, Didem
dc.contributor.buuauthorUlukaya, Engin
dc.contributor.departmentTıp Fakültesi
dc.contributor.departmentFen Edebiyet Fakültesi
dc.contributor.departmentTıbbi Biyokimya Ana Bilim Dalı
dc.contributor.departmentBiyoloji Bölümü
dc.contributor.orcid0000-0002-3781-6834
dc.contributor.researcheridAHD-2050-2022
dc.contributor.researcheridL-6682-2018
dc.contributor.researcheridK-5792-2018
dc.contributor.scopusid55693788600
dc.contributor.scopusid56422040600
dc.contributor.scopusid6602927353
dc.date.accessioned2022-11-02T06:41:47Z
dc.date.available2022-11-02T06:41:47Z
dc.date.issued2017-02
dc.description.abstractBackground: To overcome the hurdles of cisplatin, majorly its toxicity and resistance, there has been extensive search for alternative anti-cancer metal-based compounds. Here, three Cu(II)-complexes, Cu(Sal-Gly)(phen), Cu(Sal-Gly)(pheamine), Cu(Sal-Gly)(phepoxy) are characterized for their interaction with DNA, cytotoxicity and mechanism of action. Methods: The binding ability of the complexes to Calf-Thymus DNA was evaluated by competition fluorescence studies with thiazole-orange, UV-Vis and circular dichroism spectroscopic titrations. Cytotoxicity was evaluated by MTT analysis. The DNA damage was analyzed through cleavage of supercoiled DNA via agarose gel-electrophoresis, and 8-oxo-guanidine and gamma H2AX staining in cells. Apoptosis was detected via DNA condensation/fragmentation, mitochondrial membrane potential, Annexin V staining and caspase 3/7 activity. Formation of reactive oxygen species was determined by DCFDA- and GSSG/GSH-analysis. Results: Binding constants to DNA were evaluated as 1.7 x 10(6) (Cu(Sal-Gly)(phen)), 2.5 x 10(6) (Cu(Sal-Gly)(pheamine)) and 3.2 x 10(5) (Cu(Sal-Gly)(phepoxy)). All compounds induced DNA damage. Apoptosis was the main form of cell death. There was an increase in ROS, which is most likely responsible for the observed DNA-damage. Although the compounds were cytotoxic to all tested cancer cell lines, only Cu(Sal-Gly)(pheamine) displayed significantly lower toxicity towards non-cancer cells, its associated phenotypes differing from the other two Cu-complexes. Thus, Cu(Sal-Gly)(pheamine) was further assayed for molecular changes in response to drug treatment using a custom designed RT-qPCR array. Results showed that Harakiri was significantly upregulated. Presence of p53 was not required for apoptosis in response to Cu-complexes. Conclusions and general significance: These Cu-complexes, namely Cu(Sal-Gly)(pheamine), may be considered promising anticancer agents with activity in cancer cells even with deficient p53 status.
dc.description.sponsorshipPortuguese Foundation for Science and Technology UID/QUI/00100/2013
dc.description.sponsorshipIST-UTL Center of the Portuguese Mass Spectrometry Networks REM2013 - RECI/QEQ-QIN/0189/2012
dc.identifier.citationAçılan, C. vd. (2017). ''Synthesis, biological characterization and evaluation of molecular mechanisms of novel copper complexes as anticancer agents''. Biochimica et Biophysica Acta General Subjects, 1861(2), 218-134.
dc.identifier.endpage234
dc.identifier.issn0304-4165
dc.identifier.issn1872-8006
dc.identifier.issue2
dc.identifier.pubmed27773706
dc.identifier.scopus2-s2.0-84999143653
dc.identifier.startpage218
dc.identifier.urihttps://doi.org/10.1016/j.bbagen.2016.10.014
dc.identifier.urihttps://www.sciencedirect.com/science/article/pii/S0304416516303890
dc.identifier.urihttp://hdl.handle.net/11452/29316
dc.identifier.volume1861
dc.identifier.wos000392680200021
dc.indexed.wosSCIE
dc.language.isoen
dc.publisherElsevier
dc.relation.collaborationYurt dışı
dc.relation.collaborationYurt içi
dc.relation.journalBiochimica et Biophysica Acta General Subjects
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi
dc.relation.tubitakTÜBITAK
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.subjectBiochemistry & molecular biology
dc.subjectBiophysics
dc.subjectCopper complexes
dc.subjectSchiff base compounds
dc.subjectPhenanthroline
dc.subjectInteractions with DNA
dc.subjectAnti-cancer drugs
dc.subjectMechanism of cytotoxicity of Cu-compounds
dc.subjectCells in-vitro
dc.subjectSalicylideneamino acidato complexes
dc.subjectHuman cancer-cells
dc.subjectDna-binding
dc.subjectHeterocyclic bases
dc.subjectCrystal-structures
dc.subjectCleavage activity
dc.subjectTopoisomerase inhibition
dc.subjectChemical nucleases
dc.subjectOxidative stress
dc.subject.emtreeAntineoplastic agent
dc.subject.emtreeCaspase 3
dc.subject.emtreeCaspase 7
dc.subject.emtreeCopper complex
dc.subject.emtreeHistone H2AX
dc.subject.emtreeProtein p53
dc.subject.emtreeReactive oxygen metabolite
dc.subject.emtreeAntineoplastic agent
dc.subject.emtreeCalf thymus DNA
dc.subject.emtreeCopper
dc.subject.emtreeDNA
dc.subject.emtreeLipocortin 5
dc.subject.emtreeApoptosis
dc.subject.emtreeArticle
dc.subject.emtreeCancer cell line
dc.subject.emtreeControlled study
dc.subject.emtreeDNA damage
dc.subject.emtreeDNA fragmentation
dc.subject.emtreeDouble stranded DNA break
dc.subject.emtreeDrug cytotoxicity
dc.subject.emtreeDrug DNA interaction
dc.subject.emtreeDrug structure
dc.subject.emtreeDrug synthesis
dc.subject.emtreeMitochondrial membrane potential
dc.subject.emtreePriority journal
dc.subject.emtreeA-549 cell line
dc.subject.emtreeAnimal
dc.subject.emtreeBovine
dc.subject.emtreeChemistry
dc.subject.emtreeDrug effects
dc.subject.emtreeHCT 116 cell line
dc.subject.emtreeHeLa cell line
dc.subject.emtreeHuman
dc.subject.emtreeMetabolism
dc.subject.emtreeTumor cell line
dc.subject.emtreeUpregulation
dc.subject.emtreeDNA cleavage
dc.subject.meshA549 cells
dc.subject.meshAnimals
dc.subject.meshAnnexin A5
dc.subject.meshAntineoplastic agents
dc.subject.meshApoptosis
dc.subject.meshCaspase 3
dc.subject.meshCaspase 7
dc.subject.meshCattle
dc.subject.meshCell Line
dc.subject.meshTumor
dc.subject.meshCopper
dc.subject.meshDNA
dc.subject.meshDNA damage
dc.subject.meshDNA fragmentation
dc.subject.meshHCT116 cells
dc.subject.meshHeLa cells
dc.subject.meshHumans
dc.subject.meshMembrane potential
dc.subject.meshMitochondrial
dc.subject.meshReactive oxygen species
dc.subject.meshTumor suppressor protein p53
dc.subject.meshUp-regulatio
dc.subject.scopusComplex; Viscometry; Schiff Bases
dc.subject.wosBiochemistry & molecular biology
dc.subject.wosBiophysics
dc.titleSynthesis, biological characterization and evaluation of molecular mechanisms of novel copper complexes as anticancer agents
dc.typeArticle
dc.wos.quartileQ2 (Biochemistry & molecular biology)
dc.wos.quartileQ1 (Biophysics)
dspace.entity.typePublication
local.contributor.departmentFen Edebiyet Fakültesi/Biyoloji Bölümü
local.contributor.departmentTıp Fakültesi/Tıbbi Biyokimya Ana Bilim Dalı
local.indexed.atScopus
local.indexed.atWOS

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