Microbially mediated phenolic catabolites exert differential genoprotective activities in normal and adenocarcinoma cell lines

Brian Óg Murphy; Cheryl Latimer; Sara Dobani; L. Kirsty Pourshahidi; Massimilano Fontana; Nigel. G. Ternan; Gordon McDougall; Ian Rowland; Gema Pereira-Caro; Kieran M. Tuohy; Daniele Del Rio; Tahani M. Almutairi; Alan Crozier; Nenad Naumovski; Chris I. R. Gill

doi:10.1080/09637486.2024.2397055

Microbially mediated phenolic catabolites exert differential genoprotective activities in normal and adenocarcinoma cell lines

Brian Óg Murphy
, Cheryl Latimer
, Sara Dobani
, L. Kirsty Pourshahidi
, Massimilano Fontana
, Nigel. G. Ternan
, Gordon McDougall
, Ian Rowland
, Gema Pereira-Caro
, Kieran M. Tuohy
, Daniele Del Rio
, Tahani M. Almutairi
, Alan Crozier
, Nenad Naumovski
, Chris I. R. Gill

Research output: Contribution to journal › Article › peer-review

1 Citation (Scopus)

54 Downloads (Pure)

Abstract

Age-associated decline of nuclear factor erythroid 2-related factor 2 (Nrf2) activity and DNA repair efficiency leads to the accumulation of DNA damage and increased risk of cancer. Understanding the mechanisms behind increased levels of damaged DNA is crucial for developing interventions to mitigate age-related cancer risk. Associated with various health benefits, (poly)phenols and their microbially mediated phenolic catabolites represent a potential means to reduce DNA damage. Four colonic-microbiota-derived phenolic catabolites were investigated for their ability to reduce H2O2-induced oxidative DNA damage and modulate the Nrf2-Antixoidant Response Element (ARE) pathway, in normal (CCD 841 CoN) and adenocarcinoma (HT29) colonocyte cell lines. Each catabolite demonstrated significant (p < .001) genoprotective activity and modulation of key genes in the Nrf2-ARE pathway. 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 in part via upregulation of the Nrf2-ARE pathway.

Original language	English
Pages (from-to)	673-686
Number of pages	14
Journal	International Journal of Food Sciences and Nutrition
Volume	75
Issue number	7
Early online date	11 Sept 2024
DOIs	https://doi.org/10.1080/09637486.2024.2397055
Publication status	Published online - 11 Sept 2024

Bibliographical note

Publisher Copyright:
© 2024 The Author(s). Published with license by Taylor & Francis Group, LLC.

Funding

C.I.R.G. and A.C. received funding from the National Processed Raspberry Council who had no involvement in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the article for publication. G.McD. received funding from the Scottish Government’s Rural and Environment Science and Analytical Services (RESAS) Division. G.McD. received funding from BachBerry (Project No. FP7-613793).G.P.-C. was supported by a postdoctoral research contract “Juan de la Cierva Incorporación” funded by the Spanish Ministry of Economy and Competitiveness (FJCI-2015-26433). C.I.R.G., A.C., G.P.-C. and T.M.A. were funded by the Distinguished Scientist Fellowship Program (DSFP) of King Saud University, Riyadh, Saudi Arabia.

Funders	Funder number
King Saud University
National Processed Raspberry Council
FP7-613793
FJCI-2015-26433

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Benzoic acid
colonic cells
COMET assay
4-hydroxybenzoic acid
3-(3′-hydroxyphenyl)propanoic acid
3-(phenyl)propanoic acid
Humans
Hydrogen Peroxide
Phenols/pharmacology
Colon/metabolism
Oxidative Stress/drug effects
HT29 Cells
DNA Repair
Colonic Neoplasms/metabolism
NF-E2-Related Factor 2/metabolism
Cell Line, Tumor
Gastrointestinal Microbiome/drug effects
Adenocarcinoma/metabolism
DNA Damage/drug effects

Access to Document

10.1080/09637486.2024.2397055

Microbially mediated phenolic catabolites exert differential genoprotective activities in normal and adenocarcinoma cell linesFinal published version, 2.42 MBLicence: CC BY-NC-ND

Cite this

Murphy, B. Ó., Latimer, C., Dobani, S., Pourshahidi, L. K., Fontana, M., Ternan, N. G., McDougall, G., Rowland, I., Pereira-Caro, G., Tuohy, K. M., Del Rio, D., Almutairi, T. M., Crozier, A., Naumovski, N., & Gill, C. I. R. (2024). Microbially mediated phenolic catabolites exert differential genoprotective activities in normal and adenocarcinoma cell lines. International Journal of Food Sciences and Nutrition, 75(7), 673-686. Advance online publication. https://doi.org/10.1080/09637486.2024.2397055

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title = "Microbially mediated phenolic catabolites exert differential genoprotective activities in normal and adenocarcinoma cell lines",

abstract = "Age-associated decline of nuclear factor erythroid 2-related factor 2 (Nrf2) activity and DNA repair efficiency leads to the accumulation of DNA damage and increased risk of cancer. Understanding the mechanisms behind increased levels of damaged DNA is crucial for developing interventions to mitigate age-related cancer risk. Associated with various health benefits, (poly)phenols and their microbially mediated phenolic catabolites represent a potential means to reduce DNA damage. Four colonic-microbiota-derived phenolic catabolites were investigated for their ability to reduce H2O2-induced oxidative DNA damage and modulate the Nrf2-Antixoidant Response Element (ARE) pathway, in normal (CCD 841 CoN) and adenocarcinoma (HT29) colonocyte cell lines. Each catabolite demonstrated significant (p < .001) genoprotective activity and modulation of key genes in the Nrf2-ARE pathway. 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 in part via upregulation of the Nrf2-ARE pathway.",

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note = "Publisher Copyright: {\textcopyright} 2024 The Author(s). Published with license by Taylor \& Francis Group, LLC.",

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month = sep,

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doi = "10.1080/09637486.2024.2397055",

language = "English",

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Murphy, BÓ, Latimer, C, Dobani, S, Pourshahidi, LK, Fontana, M, Ternan, NG, McDougall, G, Rowland, I, Pereira-Caro, G, Tuohy, KM, Del Rio, D, Almutairi, TM, Crozier, A, Naumovski, N & Gill, CIR 2024, 'Microbially mediated phenolic catabolites exert differential genoprotective activities in normal and adenocarcinoma cell lines', International Journal of Food Sciences and Nutrition, vol. 75, no. 7, pp. 673-686. https://doi.org/10.1080/09637486.2024.2397055

TY - JOUR

T1 - Microbially mediated phenolic catabolites exert differential genoprotective activities in normal and adenocarcinoma cell lines

AU - Murphy, Brian Óg

AU - Latimer, Cheryl

AU - Dobani, Sara

AU - Pourshahidi, L. Kirsty

AU - Fontana, Massimilano

AU - Ternan, Nigel. G.

AU - McDougall, Gordon

AU - Rowland, Ian

AU - Pereira-Caro, Gema

AU - Tuohy, Kieran M.

AU - Del Rio, Daniele

AU - Almutairi, Tahani M.

AU - Crozier, Alan

AU - Naumovski, Nenad

AU - Gill, Chris I. R.

PY - 2024/9/11

Y1 - 2024/9/11

N2 - Age-associated decline of nuclear factor erythroid 2-related factor 2 (Nrf2) activity and DNA repair efficiency leads to the accumulation of DNA damage and increased risk of cancer. Understanding the mechanisms behind increased levels of damaged DNA is crucial for developing interventions to mitigate age-related cancer risk. Associated with various health benefits, (poly)phenols and their microbially mediated phenolic catabolites represent a potential means to reduce DNA damage. Four colonic-microbiota-derived phenolic catabolites were investigated for their ability to reduce H2O2-induced oxidative DNA damage and modulate the Nrf2-Antixoidant Response Element (ARE) pathway, in normal (CCD 841 CoN) and adenocarcinoma (HT29) colonocyte cell lines. Each catabolite demonstrated significant (p < .001) genoprotective activity and modulation of key genes in the Nrf2-ARE pathway. 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 in part via upregulation of the Nrf2-ARE pathway.

AB - Age-associated decline of nuclear factor erythroid 2-related factor 2 (Nrf2) activity and DNA repair efficiency leads to the accumulation of DNA damage and increased risk of cancer. Understanding the mechanisms behind increased levels of damaged DNA is crucial for developing interventions to mitigate age-related cancer risk. Associated with various health benefits, (poly)phenols and their microbially mediated phenolic catabolites represent a potential means to reduce DNA damage. Four colonic-microbiota-derived phenolic catabolites were investigated for their ability to reduce H2O2-induced oxidative DNA damage and modulate the Nrf2-Antixoidant Response Element (ARE) pathway, in normal (CCD 841 CoN) and adenocarcinoma (HT29) colonocyte cell lines. Each catabolite demonstrated significant (p < .001) genoprotective activity and modulation of key genes in the Nrf2-ARE pathway. 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 in part via upregulation of the Nrf2-ARE pathway.

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KW - colonic cells

KW - COMET assay

KW - 4-hydroxybenzoic acid

KW - 3-(3′-hydroxyphenyl)propanoic acid

KW - 3-(phenyl)propanoic acid

KW - Humans

KW - Hydrogen Peroxide

KW - Phenols/pharmacology

KW - Colon/metabolism

KW - Oxidative Stress/drug effects

KW - HT29 Cells

KW - DNA Repair

KW - Colonic Neoplasms/metabolism

KW - NF-E2-Related Factor 2/metabolism

KW - Cell Line, Tumor

KW - Gastrointestinal Microbiome/drug effects

KW - Adenocarcinoma/metabolism

KW - DNA Damage/drug effects

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UR - https://www.scopus.com/pages/publications/85203554914

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DO - 10.1080/09637486.2024.2397055

M3 - Article

C2 - 39261459

SN - 0963-7486

VL - 75

SP - 673

EP - 686

JO - International Journal of Food Sciences and Nutrition

JF - International Journal of Food Sciences and Nutrition

IS - 7

ER -

Microbially mediated phenolic catabolites exert differential genoprotective activities in normal and adenocarcinoma cell lines

Abstract

Bibliographical note

Funding

UN SDGs

Keywords

Access to Document

Other files and links

Fingerprint

VALGUT: phenyl-ϒ-valerolactones are microbiota-derived compounds that can impact gut health

Cite this

Microbially mediated phenolic catabolites exert differential genoprotective activities in normal and adenocarcinoma cell lines

Abstract

Bibliographical note

Funding

UN SDGs

Keywords

Access to Document

Other files and links

Fingerprint

Student theses

VALGUT: phenyl-ϒ-valerolactones are microbiota-derived compounds that can impact gut health

Cite this