TY - JOUR
T1 - The NR4A agonist, Cytosporone B, attenuates pro-inflammatory mediators in human colorectal cancer tissue ex vivo
AU - Ismaiel, Mohamed
AU - Murphy, Brenda
AU - Aldhafiri, Sarah
AU - Giffney, Hugh E.
AU - Thornton, Kevin
AU - Mukhopadhya, Anindya
AU - Keogh, Ciara E.
AU - Fattah, Sarinj
AU - Mohan, Helen M.
AU - Cummins, Eoin P.
AU - Murphy, Evelyn P.
AU - Winter, Des C.
AU - Crean, Daniel
N1 - Publisher Copyright:
© 2021 The Authors
PY - 2021/5/21
Y1 - 2021/5/21
N2 - 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 μM CsnB did not adversely affect tissue integrity as measured using transepithelial electrical resistance, histology and crypt height. Subsequently, we reveal through the use of a cytokine/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-1β, IL-8 and TNFα). 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.
AB - 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 μM CsnB did not adversely affect tissue integrity as measured using transepithelial electrical resistance, histology and crypt height. Subsequently, we reveal through the use of a cytokine/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-1β, IL-8 and TNFα). 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.
KW - Colorectal cancer
KW - Cytosporone B
KW - Inflammation
KW - NR4A
UR - http://www.scopus.com/inward/record.url?scp=85103431557&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2021.03.110
DO - 10.1016/j.bbrc.2021.03.110
M3 - Article
C2 - 33798945
AN - SCOPUS:85103431557
SN - 0006-291X
VL - 554
SP - 179
EP - 185
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
ER -