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dc.contributor.authorMontagner, Diego
dc.contributor.authorGandin, Valentina
dc.contributor.authorMarzano, Cristina
dc.contributor.authorErxleben, Andrea
dc.date.accessioned2017-05-23T15:32:32Z
dc.date.available2017-05-23T15:32:32Z
dc.date.issued2015-01-26
dc.identifier.citationMontagner, Diego, Gandin, Valentina, Marzano, Cristina, & Erxleben, Andrea. (2015). DNA damage and induction of apoptosis in pancreatic cancer cells by a new dinuclear bis(triazacyclonane) copper complex. Journal of Inorganic Biochemistry, 145, 101-107. doi: https://doi.org/10.1016/j.jinorgbio.2015.01.013en_IE
dc.identifier.issn1873-3344
dc.identifier.urihttp://hdl.handle.net/10379/6540
dc.description.abstractThe dinuclear copper(II) complex [Cu-2{bcmp(-H)}(mu-OH)](NO3)(2)center dot H2O (1, bcmp = 2,6-bis(1,4,7-triazacyclonon-1-ylmethyl)-4-methylphenol) has been synthesized and characterized by electrospray ionization mass spectrometry, potentiometric titration and cyclovoltammetry. The X-ray structure of the analogous perchlorate salt [Cu-2{bcmp(-H)}(mu-OH)](ClO4)(2)center dot 2.5H(2)O (2) was determined. Cytotoxicity studies showed very promising activity of 1 against various pancreatic tumor cell lines with IC50 values comparable or even lower than those of cisplatin. The Cu complex displayed low toxicity against a human non-tumor cell line (HEM 293) demonstrating selectivity for cancer cells. 1 converts supercoiled pUC19 plasmid DNA into the nicked form at micromolar concentrations in the absence of added reductants. A detailed kinetic study on the hydrolysis of the DNA model bis(2,4-dinitrophenyl) phosphate (BDNPP) has been performed. 1 hydrolyses BDNPP with a second order rate constant of 0.047 M s(-1) at pH 8 and 40 degrees C. Finally, single cell electrophoresis (comet assay) and fluorescence microscopy analysis showed that 1 interacts with cellular DNA and induces apoptotic cell death of Capan-1 pancreatic cancer cells. Western blotting analysis indicated that the Cu complex activates the p53 dependent pathway of apoptosis. (C) 2015 Elsevier Inc. All rights reserved.en_IE
dc.description.sponsorshipFinancial supports from the European Commission and Science Foundation Ireland (Marie Curie FP7-IEF to D.M., Stokes Lectureship to A.E., grant no. 07/SK/B1225b) and from the University of Padova (Progetto di Ateneo CPDA121973/12) are gratefully acknowledged.en_IE
dc.formatapplication/pdfen_IE
dc.language.isoenen_IE
dc.publisherElsevieren_IE
dc.relation.ispartofJournal Of Inorganic Biochemistryen
dc.subjectCopperen_IE
dc.subjectCytotoxicityen_IE
dc.subjectDNA damageen_IE
dc.subjectMetallodrugsen_IE
dc.subject1,10-PHENANTHROLINEen_IE
dc.subjectPhosphatase like activityen_IE
dc.subjectPurple acid phosphatasesen_IE
dc.subjectDicopper(II) complexen_IE
dc.subjectCrystal structuresen_IE
dc.subjectAnticancer agentsen_IE
dc.subjectMetal complexesen_IE
dc.subjectHydrolysisen_IE
dc.subjectLigandsen_IE
dc.subjectCleavageen_IE
dc.subject1, 10-phenanthrolineen_IE
dc.titleDNA damage and induction of apoptosis in pancreatic cancer cells by a new dinuclear bis(triazacyclonane) copper complexen_IE
dc.typeArticleen_IE
dc.date.updated2017-05-18T12:39:52Z
dc.identifier.doi10.1016/j.jinorgbio.2015.01.013
dc.local.publishedsourcehttps://doi.org/10.1016/j.jinorgbio.2015.01.013en_IE
dc.description.peer-reviewedpeer-reviewed
dc.contributor.funder|~|
dc.internal.rssid9391720
dc.local.contactAndrea Erxleben, School Of Chemistry, Room 150, Arts/Science Building, Nui Galway. 2483 Email: andrea.erxleben@nuigalway.ie
dc.local.copyrightcheckedNo
dc.local.versionACCEPTED
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