Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Microbially-Mediated Phenolic Catabolites Exert Differential Geno-Protective Activities in Normal and Adenocarcinoma Cell Lines

BrianÓg Murphy
ORCID logo ,
Cheryl Latimer
,
Sara Dobani
,
L. Kirsty Pourshahidi
ORCID logo ,
Massimiliano Fontana
,
Nigel George Ternan
ORCID logo ,
Gordon J McDougall
ORCID logo ,
Ian Rowland
ORCID logo ,
Gema Pereira-Caro
ORCID logo ,
Kieran Tuohy
,
Daniele Del Rio
ORCID logo ,
Tahani Mazyad Almutairi
,
Alan Crozier
,
Chris I. R. Gill
*
Version 1 : Received: 7 August 2023 / Approved: 8 August 2023 / Online: 9 August 2023 (08:48:35 CEST)

How to cite: Murphy, B.; Latimer, C.; Dobani, S.; Pourshahidi, L.K.; Fontana, M.; Ternan, N.G.; McDougall, G.J.; Rowland, I.; Pereira-Caro, G.; Tuohy, K.; Rio, D.D.; Mazyad Almutairi, T.; Crozier, A.; Gill, C.I.R. Microbially-Mediated Phenolic Catabolites Exert Differential Geno-Protective Activities in Normal and Adenocarcinoma Cell Lines. Preprints 2023, 2023080755. https://doi.org/10.20944/preprints202308.0755.v1 Murphy, B.; Latimer, C.; Dobani, S.; Pourshahidi, L.K.; Fontana, M.; Ternan, N.G.; McDougall, G.J.; Rowland, I.; Pereira-Caro, G.; Tuohy, K.; Rio, D.D.; Mazyad Almutairi, T.; Crozier, A.; Gill, C.I.R. Microbially-Mediated Phenolic Catabolites Exert Differential Geno-Protective Activities in Normal and Adenocarcinoma Cell Lines. Preprints 2023, 2023080755. https://doi.org/10.20944/preprints202308.0755.v1

Abstract

Ageing is associated with a decline in both Nrf2 activity and DNA repair efficiency, leading to the accumulation of DNA damage and an increased risk of cancer. Understanding the mechanisms behind the increased level of damaged DNA during ageing is crucial for developing interventions to mitigate age-related cancer risk and improve overall health in older individuals. (Poly)phenols are plant-derived bioactive compounds that undergo metabolism into simpler phenolic catabolites following ingestion. While these compounds have been associated with various health benefits, further analysis of their bioavailable catabolites is necessary. To this end, four phenolic catabolites derived from colonic microbiota were investigated for their ability to reduce DNA damage in response to oxidative challenge and modulate the Nrf2-Antixoidant Response Element pathway. Normal and adenocarcinoma colonocyte cell lines (CCD 841 CoN, & HT29 respectively) were exposed to sub cytotoxic concentrations (>10 µM,) of hydroxylated (4-hydroxybenzoic acid, 3-(3’-hydroxyphenyl) propionic acid) and non-hydroxylated (benzoic acid or 3-phenylpropionic acid) phenolic acids. Using the COMET assay, each catabolite demonstrated significant (p<0.001) geno-protective activity, albeit with varying potency. They also significantly modulated expression of key genes in the Nrf2-ARE pathway, including Nrf2, Heme oxygenase-1 (HO-1), and NAD(P)H dehydrogenase quinone 1 (NQO1). Hydroxylation of the phenolic acids appeared to have a limited effect with respect to bioactivity. Overall, the colon derived phenolic metabolites, when assessed at physiologically relevant concentrations, reduced DNA damage in both normal and adenocarcinoma colonic cells in response to oxidative challenge, mediated – at least in part via upregulation of the Nrf2-ARE pathway.

Keywords

3-(3′-Hydroxyphenyl)propanoic acid; 3-(Phenyl)propanoic acid; 4-Hydroxybenzoic acid; Benzoic acid; Colonic cells; COMET assay; Nrf2 pathway; Phenolic catabolites

Subject

Biology and Life Sciences, Life Sciences

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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