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dc.contributor.authorTolan, Dina
dc.contributor.authorGandin, Valentina
dc.contributor.authorMorrison, Liam
dc.contributor.authorEl-Nahas, Ahmed
dc.contributor.authorMarzano, Cristina
dc.contributor.authorMontagner, Diego
dc.contributor.authorErxleben, Andrea
dc.date.accessioned2017-05-23T13:23:10Z
dc.date.available2017-05-23T13:23:10Z
dc.date.issued2016-06-11
dc.identifier.citationTolan, Dina, Gandin, Valentina, Morrison, Liam, El-Nahas, Ahmed, Marzano, Cristina, Montagner, Diego, & Erxleben, Andrea. (2016). Oxidative Stress Induced by Pt(IV) Pro-drugs Based on the Cisplatin Scaffold and Indole Carboxylic Acids in Axial Position. Scientific Reports, 6, 29367. doi: 10.1038/srep29367 https://www.nature.com/articles/srep29367#supplementary-informationen_IE
dc.identifier.issn2045-2322
dc.identifier.urihttp://hdl.handle.net/10379/6536
dc.description.abstractThe use of Pt(IV) complexes as pro-drugs that are activated by intracellular reduction is a widely investigated approach to overcome the limitations of Pt(II) anticancer agents. A series of ten mono- and bis-carboxylated Pt(IV) complexes with axial indole-3-acetic acid (IAA) and indole-3-propionic acid (IPA) ligands were synthesized and characterized by elemental analysis, ESI-MS, FT-IR, H-1 and Pt-195 NMR spectroscopy. Cellular uptake, DNA platination and cytotoxicity against a panel of human tumor cell lines were evaluated. All the complexes are able to overcome cisplatin-resistance and the most potent complex, cis, cis, trans-[Pt(NH3)(2)Cl-2(IPA)(OH)] was on average three times more active than cisplatin. Mechanistic studies revealed that the trend in cytotoxicity of the Pt(IV) complexes is primarily consistent with their ability to accumulate into cancer cells and to increase intracellular basal reactive oxygen species levels, which in turn results in the loss of mitochondrial membrane potential and apoptosis induction. The role of the indole acid ligand as a redox modulator is discussed.en_IE
dc.description.sponsorshipD.T. would like to thank the Egyptian Ministry of Higher Education (MoHE) for providing the financial support (PhD scholarship) for this research. This work was partially financially supported by the University of Padova (Grants 60A04-0443, 60A04-3189 and 60A04-4015/15).en_IE
dc.formatapplication/pdfen_IE
dc.language.isoenen_IE
dc.publisherNature Publishing Groupen_IE
dc.relation.ispartofScientific Reportsen
dc.rightsAttribution-NonCommercial-NoDerivs 3.0 Ireland
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/3.0/ie/
dc.subjectPlatinum(IV) anticancer complexesen_IE
dc.subjectOvarian cancer cellsen_IE
dc.subjectTetracarboxylatoplatinum(IV) complexesen_IE
dc.subjectCyclooxygenase inhibitorsen_IE
dc.subjectIndole-3-propionic aciden_IE
dc.subjectIndole-3-acetic acidsen_IE
dc.subjectLipid peroxidationen_IE
dc.subjectCytotoxic activityen_IE
dc.subjectIcp-msen_IE
dc.subjectAgentsen_IE
dc.titleOxidative stress induced by Pt(IV) pro-drugs based on the cisplatin scaffold and indole carboxylic acids in axial positionen_IE
dc.typeArticleen_IE
dc.date.updated2017-05-18T08:07:06Z
dc.identifier.doi10.1038/srep29367
dc.local.publishedsourcehttp://dx.doi.org/10.1038/srep29367en_IE
dc.description.peer-reviewedpeer-reviewed
dc.contributor.funder|~|
dc.internal.rssid11422115
dc.local.contactAndrea Erxleben, School Of Chemistry, Room 150, Arts/Science Building, Nui Galway. 2483 Email: andrea.erxleben@nuigalway.ie
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