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dc.contributor.authorClaudius, AK
dc.contributor.authorKankipati, CS
dc.contributor.authorKilari, RS
dc.contributor.authorHassan, S
dc.contributor.authorGuest, K
dc.contributor.authorRussell, ST
dc.contributor.authorPerry, CJ
dc.contributor.authorStark, LA
dc.contributor.authorNicholl, ID
dc.date.accessioned2019-06-03T14:42:57Z
dc.date.available2019-06-03T14:42:57Z
dc.date.issued2014-07-31
dc.identifier.citationClaudius, A-K., Kankipati, C. S., Kilari, R. S., Hassan, S., Guest, K., Russell, S. T., ... Nicholl, I. D. (2014). Identification of aspirin analogues that repress NF-κB signalling and demonstrate anti-proliferative activity towards colorectal cancer in vitro and in vivo. Oncology Reports, 32(4), 1670-1680. https://doi.org/10.3892/or.2014.3373en
dc.identifier.pmid25109257
dc.identifier.doi10.3892/or.2014.3373en
dc.identifier.urihttp://hdl.handle.net/2436/622397
dc.description.abstractSubstantial evidence indicates that aspirin and related non-steroidal anti-inflammatory drugs (NSAIDs) have potential as chemopreventative/therapeutic agents. However, these agents cannot be universally recommended for prevention purposes due to their potential side-effect profiles. Here, we compared the growth inhibitory and mechanistic activity of aspirin to two novel analogues, diaspirin (DiA) and fumaryl diaspirin (F-DiA). We found that the aspirin analogues inhibited cell proliferation and induced apoptosis of colorectal cancer cells at significantly lower doses than aspirin. Similar to aspirin, we found that an early response to the analogues was a reduction in levels of cyclin D1 and stimulation of the NF-κB pathway. This stimulation was associated with a significant reduction in basal levels of NF-κB transcriptional activity, in keeping with previous data for aspirin. However, in contrast to aspirin, DiA and F-DiA activity was not associated with nucleolar accumulation of RelA. For all assays, F-DiA had a more rapid and significant effect than DiA, identifying this agent as particularly active against colorectal cancer. Using a syngeneic colorectal tumour model in mice, we found that, while both agents significantly inhibited tumour growth in vivo, this effect was particularly pronounced for F-DiA. These data identify two compounds that are active against colorectal cancer in vitro and in vivo. They also identify a potential mechanism of action of these agents and shed light on the chemical structures that may be important for the antitumour effects of aspirin.en
dc.description.sponsorshipThis project was supported by funding from the Research Institute in Healthcare Science, University of Wolverhampton (IDN) and by the AICR (10-0158) (LAS).en
dc.formatapplication/PDFen
dc.languageeng
dc.language.isoenen
dc.publisherSpandidos Publicationsen
dc.relation.urlhttps://www.spandidos-publications.com/10.3892/or.2014.3373en
dc.subjectCell Line, Tumoren
dc.subjectAnimalsen
dc.subjectHumansen
dc.subjectMiceen
dc.subjectMice, Nudeen
dc.subjectAdenocarcinomaen
dc.subjectColorectal Neoplasmsen
dc.subjectAspirinen
dc.subjectNF-kappa Ben
dc.subjectAnti-Inflammatory Agents, Non-Steroidalen
dc.subjectDrug Screening Assays, Antitumoren
dc.subjectXenograft Model Antitumor Assaysen
dc.subjectSignal Transductionen
dc.subjectCell Cycleen
dc.subjectApoptosisen
dc.subjectCell Proliferationen
dc.subjectTranscription Factor RelAen
dc.subjectCyclin Den
dc.titleIdentification of aspirin analogues that repress NF-κB signalling and demonstrate anti-proliferative activity towards colorectal cancer in vitro and in vivoen
dc.typeJournal articleen
dc.identifier.eissn1791-2431
dc.identifier.journalOncology Reportsen
dc.date.updated2019-05-24T15:33:12Z
dc.contributor.institutionEdinburgh Cancer Research Centre and MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK.
pubs.place-of-publicationGreece
dc.date.accepted2014-06-26
rioxxterms.funderUniversity of Wolverhamptonen
rioxxterms.identifier.project10-0158en
rioxxterms.identifier.projectMR/J001481/1en
rioxxterms.identifier.projectETM/154en
rioxxterms.identifier.projectUOW030619INen
rioxxterms.versionVoRen
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/en
rioxxterms.licenseref.startdate2019-06-03en
dc.source.volume32
dc.source.issue4
dc.source.beginpage1670
dc.source.endpage1680
dc.description.versionPublished version
refterms.dateFCD2019-06-03T14:42:42Z
refterms.versionFCDVoR
refterms.dateFOA2019-06-03T14:42:58Z


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