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The NR4A agonist, cytosporone B, attenuates pro-inflammatory mediators in human colorectal cancer tissue ex vivo

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dc.contributor.author Ismaiel, Mohamed
dc.contributor.author Murphy, Brenda
dc.contributor.author Aldhafiri, Sarah
dc.contributor.author Giffney, Hugh E.
dc.contributor.author Thornton, Kevin
dc.contributor.author Mukhopadhya, Anindya
dc.contributor.author Keogh, Ciara E.
dc.contributor.author Fattah, Sarinj
dc.contributor.author Mohan, Helen M.
dc.contributor.author Cummins, Eoin P.
dc.contributor.author Murphy, Evelyn P
dc.contributor.author Winter, Des C.
dc.contributor.author Crean, Daniel
dc.date.accessioned 2021-04-08T10:48:15Z
dc.date.available 2021-04-08T10:48:15Z
dc.date.issued 2021
dc.identifier.uri http://hdl.handle.net/10344/9974
dc.description peer-reviewed en_US
dc.description.abstract Inflammation is a pivotal pathological factor in colorectal cancer (CRC) initiation and progression, and modulating this inflammatory state has the potential to ameliorate disease progression. NR4A receptors have emerged as key regulators of inflammatory pathways that are important in CRC. Here, we have examined the effect of NR4A agonist, Cytosporone B (CsnB), on colorectal tissue integrity and its effect on the inflammatory profile in CRC tissue ex vivo. Here, we demonstrate concentrations up 100 mM CsnB did not adversely affect tissue integrity as measured using transepithelial electrical resistance, histology and crypt height. Subsequently, we reveal through the use of acytokine/chemokine array, ELISA and qRT-PCR analysis that multiple pro-inflammatory mediators were significantly increased in CRC tissue compared to control tissue, which were then attenuated with the addition of CsnB (such as IL-1b, IL-8 and TNFa). Lastly, stratification of the data revealed that CsnB especially alters the inflammatory profile of tumours derived from males who had not undergone chemoradiotherapy. Thus, this study demonstrates that NR4A agonist CsnB does not adversely affect colon tissue structure or functionality and can attenuate the pro-inflammatory state of human CRC tissue ex vivo en_US
dc.language.iso eng en_US
dc.publisher Elsevier en_US
dc.relation.ispartofseries Biochemical and Biophysical Research Communications;554, pp. 179-185
dc.subject Colorectal cancer en_US
dc.subject Inflammation en_US
dc.subject NR4A en_US
dc.title The NR4A agonist, cytosporone B, attenuates pro-inflammatory mediators in human colorectal cancer tissue ex vivo en_US
dc.type info:eu-repo/semantics/article en_US
dc.type.supercollection all_ul_research en_US
dc.type.supercollection ul_published_reviewed en_US
dc.identifier.doi 10.1016/j.bbrc.2021.03.110
dc.contributor.sponsor Saudi Arabian Cultural Bureau en_US
dc.contributor.sponsor UCD en_US
dc.rights.accessrights info:eu-repo/semantics/openAccess en_US


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