dc.contributor.author | Montagner, Diego | |
dc.contributor.author | Gandin, Valentina | |
dc.contributor.author | Marzano, Cristina | |
dc.contributor.author | Erxleben, Andrea | |
dc.date.accessioned | 2017-05-23T15:32:32Z | |
dc.date.available | 2017-05-23T15:32:32Z | |
dc.date.issued | 2015-01-26 | |
dc.identifier.citation | Montagner, 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.2015.01.013 | en_IE |
dc.identifier.issn | 1873-3344 | |
dc.identifier.uri | http://hdl.handle.net/10379/6540 | |
dc.description.abstract | The 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.sponsorship | Financial 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.format | application/pdf | en_IE |
dc.language.iso | en | en_IE |
dc.publisher | Elsevier | en_IE |
dc.relation.ispartof | Journal Of Inorganic Biochemistry | en |
dc.rights | Attribution-NonCommercial-NoDerivs 3.0 Ireland | |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/3.0/ie/ | |
dc.subject | Copper | en_IE |
dc.subject | Cytotoxicity | en_IE |
dc.subject | DNA damage | en_IE |
dc.subject | Metallodrugs | en_IE |
dc.subject | 1,10-PHENANTHROLINE | en_IE |
dc.subject | Phosphatase like activity | en_IE |
dc.subject | Purple acid phosphatases | en_IE |
dc.subject | Dicopper(II) complex | en_IE |
dc.subject | Crystal structures | en_IE |
dc.subject | Anticancer agents | en_IE |
dc.subject | Metal complexes | en_IE |
dc.subject | Hydrolysis | en_IE |
dc.subject | Ligands | en_IE |
dc.subject | Cleavage | en_IE |
dc.subject | 1, 10-phenanthroline | en_IE |
dc.title | DNA damage and induction of apoptosis in pancreatic cancer cells by a new dinuclear bis(triazacyclonane) copper complex | en_IE |
dc.type | Article | en_IE |
dc.date.updated | 2017-05-18T12:39:52Z | |
dc.identifier.doi | 10.1016/j.jinorgbio.2015.01.013 | |
dc.local.publishedsource | https://doi.org/10.1016/j.jinorgbio.2015.01.013 | en_IE |
dc.description.peer-reviewed | peer-reviewed | |
dc.contributor.funder | |~| | |
dc.internal.rssid | 9391720 | |
dc.local.contact | Andrea Erxleben, School Of Chemistry, Room 150, Arts/Science Building, Nui Galway. 2483 Email: andrea.erxleben@nuigalway.ie | |
dc.local.copyrightchecked | No | |
dc.local.version | ACCEPTED | |
nui.item.downloads | 429 | |