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

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journal contribution
posted on 2021-04-08, 10:48 authored by Mohamed Ismaiel, Brenda Murphy, Sarah Aldhafiri, Hugh E. Giffney, Kevin Thornton, Anindya Mukhopadhya, Ciara E. Keogh, Sarinj Fattah, Helen M. Mohan, Eoin P. Cummins, Evelyn P. Murphy, Desmond C. Winter, Daniel Crean
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

History

Publication

Biochemical and Biophysical Research Communications;554, pp. 179-185

Publisher

Elsevier

Note

peer-reviewed

Other Funding information

Saudi Arabian Cultural Bureau, UCD

Language

English

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