The cytotoxicity and synergistic potential of aspirin and aspirin analogues towards oesophageal and colorectal cancer

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dc.contributor.authorKilari, R.S.
dc.contributor.authorBashir, A.I.J.
dc.contributor.authorDevitt, A.
dc.contributor.authorPerry, C.J.
dc.contributor.authorSafrany, C.J.
dc.contributor.authorNicholl, Iain D.
dc.date.accepted2018-10-31
dc.date.accessioned2019-03-14T09:50:29Z
dc.date.available2019-03-14T09:50:29Z
dc.date.issued2018-11-12
dc.description.abstractBACKGROUND: Oesophageal cancer (OC) is a deadly cancer because of its aggressive nature with survival rates that have barely improved in decades. Epidemiologic studies have shown that low-dose daily intake of aspirin can decrease the incidence of OC. METHODS: The toxicity of aspirin and aspirin derivatives to OC and a colorectal cancer (CRC) cell line were investigated in the presence and absence of platins. RESULTS: The data in this study show the effects of a number of aspirin analogues and aspirin on OC cell lines that originally presented as squamous cell carcinoma (SSC) and adenocarcinoma (ADC). The aspirin analogues fumaryldiaspirin (PN517) and the benzoylsalicylates (PN524, PN528 and PN529), were observed to be more toxic against the OC cell lines than aspirin. Both quantitative and qualitative apoptosis experiments reveal that these compounds largely induce apoptosis, although some necrosis was evident with PN528 and PN529. Failure to recover following the treatment with these analogues emphasized that these drugs are largely cytotoxic in nature. The OE21 (SSC) and OE33 (ADC) cell lines were more sensitive to the aspirin analogues compared to the Flo-1 cell line (ADC). A non-cancerous oesophageal primary cells NOK2101, was used to determine the specificity of the aspirin analogues and cytotoxicity assays revealed that analogues PN528 and PN529 were selectively toxic to cancer cell lines, whereas PN508, PN517 and PN524 also induced cell death in NOK2101. In combination index testing synergistic interactions of the most promising compounds, including aspirin, with cisplatin, oxaliplatin and carboplatin against the OE33 cell line and the SW480 CRC cell line were investigated. Compounds PN517 and PN524, and to a lesser extent PN528, synergised with cisplatin against OE33 cells. Cisplatin and oxaliplatin synergised with aspirin and PN517 when tested against the SW480 cell line. CONCLUSION: These findings indicate the potential and limitations of aspirin and aspirin analogues as chemotherapeutic agents against OC and CRC when combined with platins.en
dc.formatapplication/PDFen
dc.identifier.citationKilari, R.S. et al The cytotoxicity and synergistic potential of aspirin and aspirin analogues towards oesophageal and colorectal cancer, Current Clinical Pharmacology, 2019, 14, 1-10en
dc.identifier.doi10.2174/1574884713666181112141151
dc.identifier.issn1574-8847en
dc.identifier.journalCurrent Clinical Pharmacologyen
dc.identifier.pmid30417794
dc.identifier.urihttp://hdl.handle.net/2436/622200
dc.language.isoenen
dc.publisherBenthamen
dc.relation.urlhttp://www.eurekaselect.com/167265/articleen
dc.rightsAttribution-NonCommercial-NoDerivs 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/us/*
dc.source.beginpage1
dc.source.endpage10
dc.source.volume14
dc.subjectcolorectal canceren
dc.subjectoesophageal canceren
dc.subjectfumaryl diaspirinen
dc.subjectaspirinen
dc.subjectplatinsen
dc.subjectesophageal canceren
dc.subjectsynergyen
dc.titleThe cytotoxicity and synergistic potential of aspirin and aspirin analogues towards oesophageal and colorectal canceren
dc.typeJournal article
refterms.dateFCD2019-03-14T09:50:30Z
refterms.versionFCDAM
rioxxterms.funderUniversity of Wolverhamptonen
rioxxterms.identifier.projectUOW140319INen
rioxxterms.licenseref.startdate2019-11-12en
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/en
rioxxterms.versionAMen
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