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A comparative study of genoprotective activity of phenolic catabolites between normal and adenocarcinoma colonic cells in vitro

Published online by Cambridge University Press:  05 September 2023

B.O. Murphy ,
C. Latimer ,
S. Dobani ,
L.K. Pourshahidi ,
N.G. Ternan ,
R. Lawther ,
G. McDougall ,
I. Rowland ,
G. Pereira-Caro  and
K.M. Tuohy
...Show all authors
B.O. Murphy
Affiliation:
Nutrition Innovation Centre for Food and Health (NICHE), Ulster University, Coleraine, UK
C. Latimer
Affiliation:
Nutrition Innovation Centre for Food and Health (NICHE), Ulster University, Coleraine, UK
S. Dobani
Affiliation:
Nutrition Innovation Centre for Food and Health (NICHE), Ulster University, Coleraine, UK
L.K. Pourshahidi
Affiliation:
Nutrition Innovation Centre for Food and Health (NICHE), Ulster University, Coleraine, UK
N.G. Ternan
Affiliation:
Nutrition Innovation Centre for Food and Health (NICHE), Ulster University, Coleraine, UK
R. Lawther
Affiliation:
Altnagelvin Area Hospital, Londonderry, UK
G. McDougall
Affiliation:
Environmental and Biochemical Sciences Department, The James Hutton Institute, Invergowrie, Dundee, UK
I. Rowland
Affiliation:
Department of Food and Nutritional Sciences, University of Reading, Reading, UK
G. Pereira-Caro
Affiliation:
Department of Food Science and Health, IFAPA-Alameda Del Obispo, Córdoba, Spain
K.M. Tuohy
Affiliation:
School of Food Science and Nutrition, University of Leeds, Leeds, United Kingdom
D. Del Rio
Affiliation:
Human Nutrition Unit, Department of Food and Drug, University of Parma, Parma, Italy
A. Crozier
Affiliation:
Department of Chemistry, King Saud University Riyadh, Saudi Arabia.
C.I.R Gill
Affiliation:
Nutrition Innovation Centre for Food and Health (NICHE), Ulster University, Coleraine, UK
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Abstract

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Proceedings of the Nutrition Society , Volume 82 , Issue OCE4: Irish Section Conference 2023, 14–16 June 2023, Understanding the role of sex and gender in nutrition research , 2023 , E266
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Copyright © The Author(s), 2023. Published by Cambridge University Press on behalf of The Nutrition Society

(Poly)phenols are plant-derived bioactive compounds abundant in human diet,(Reference Lorenzo, Colombo and Biella1,Reference Aravind, Wichienchot and Tsao2) that are largely metabolised to simpler phenolic catabolites upon ingestion(Reference Bresciani, Brindani and Ludwig3–5). These compounds have been attributed with several beneficial effects on human health,(Reference Rio, Rodriguez-Mateos and Spencer4,Reference Latimer, Ternan and Pourshahidi6,Reference Luca, Macovei and Bujor7) but further analyses on the properties of these bioavailable catabolites is needed. To this end, four previously identified microbiota mediated phenolic catabolites were assessed for their anti- genotoxicity and ability to activate the Nrf2-pathway, which provides protection against oxidative stress.

Normal and adenocarcinoma colonocyte cell lines were cultured with either 4-hydroxybenzoic acid (HBA), benzoic acid (BA), 3-(3-hydroxyphenyl) propionic acid (3’HPPA), or 3- phenylpropionic acid (3PPA) at 10 μM, 50 μM, and 100 μM for 24 hours. The phenolic catabolites were determined to be non-cytotoxic in both cell lines up to 100 μM.

Each phenolic catabolite exhibited significant (p < 0.001) genoprotective activity (COMET assay) in both cell lines but with varying potency. Furthermore, gene expression (qPCR) studies showed that exposure to the phenolics altered the expression of key genes in the nuclear factor erythroid-derived 2-like 2 (Nrf2)-antioxidant response pathway, namely Nrf2, heme oxygenase 1 (HO-1), and NAD(P)H dehydrogenase quinone 1 (NQO1). Specifically, treatment of either cell line with the phenolics at 50 μM and 100 μM resulted in significant increases (ranging from 1.46-fold to 3.17-fold, p <0.001) in gene expression for most genes of interest, and there appears to be some correlation between the degree of genotoxic protection offered and the elevation of expression of specific genes.

To conclude, microbiota mediated phenolic metabolites at physiologically relevant concentrations can reduce DNA damage in both normal and adenocarcinoma colonic cells and may be in part mediated by an upregulation of the Nrf2-ARE pathway.

References

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Bresciani, P, Brindani, L, Ludwig, NA et al. (2019) Natural Product Reports 36, 714–752.Google Scholar
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