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dc.contributor.authorAllison, Simon J.
dc.contributor.authorSadiq, Maria
dc.contributor.authorBaronou, Efstathia
dc.contributor.authorCooper, Patricia A.
dc.contributor.authorDunnill, C.
dc.contributor.authorGeorgopoulos, N.T.
dc.contributor.authorLatif, A.
dc.contributor.authorShepherd, S.L.
dc.contributor.authorShnyder, Steven D.
dc.contributor.authorStratford, I.J.
dc.contributor.authorWheelhouse, Richard T.
dc.contributor.authorWillans, C.
dc.contributor.authorPhillips, Roger M.
dc.date.accessioned2017-05-10T11:25:07Z
dc.date.available2017-05-10T11:25:07Z
dc.date.issued2017-09
dc.identifier.citationAllison SJ, Sadiq M, Baronou E et al (2017) Preclinical anti-cancer activity and multiple mechanisms of action of a cationic silver complex bearing N-heterocyclic carbine ligands. Cancer Letters. 403: 98-107.en_US
dc.identifier.urihttp://hdl.handle.net/10454/11960
dc.descriptionYesen_US
dc.description.abstractOrganometallic complexes offer the prospect of targeting multiple pathways that are important in cancer biology. Here, the preclinical activity and mechanism(s) of action of a silver-bis(N-heterocyclic carbine) complex (Ag8) were evaluated. Ag8 induced DNA damage via several mechanisms including topoisomerase I/II and thioredoxin reductase inhibition and induction of reactive oxygen species. DNA damage induction was consistent with cytotoxicity observed against proliferating cells and Ag8 induced cell death by apoptosis. Ag8 also inhibited DNA repair enzyme PARP1, showed preferential activity against cisplatin resistant A2780 cells and potentiated the activity of temozolomide. Ag8 was substantially less active against non-proliferating non-cancer cells and selectively inhibited glycolysis in cancer cells. Ag8 also induced significant anti-tumour effects against cells implanted intraperitoneally in hollow fibres but lacked activity against hollow fibres implanted subcutaneously. Thus, Ag8 targets multiple pathways of importance in cancer biology, is less active against non-cancer cells and shows activity in vivo in a loco-regional setting.en_US
dc.description.sponsorshipRMP and MS funded by Yorkshire Cancer Research (pump priming grant BPP 046). IJS and AL funded by NIHR Research & Innovation Division, Strategic Project Funding 2013 and Manchester Pharmacy School Fellowship.en_US
dc.language.isoenen_US
dc.relation.isreferencedbyhttp://dx.doi.org/10.1016/j.canlet.2017.04.041
dc.rights© 2017 Elsevier. Reproduced in accordance with the publisher's self-archiving policy. This manuscript version is made available under the CC-BY-NC-ND 4.0 license.en_US
dc.subjectSilver-N-heterocyclic carbene; Thioredoxin reductase inhibitor; Topoisomerase inhibitor; PARP1 inhibitor; Glycolytic inhibitoren_US
dc.titlePreclinical anti-cancer activity and multiple mechanisms of action of a cationic silver complex bearing N-heterocyclic carbene ligandsen_US
dc.status.refereedYesen_US
dc.date.Accepted2017-04-29
dc.date.application2017-06-15
dc.typeArticleen_US
dc.type.versionAccepted Manuscripten_US
refterms.dateFOA2018-06-16T00:00:00Z


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