Microbially mediated phenolic catabolites exert differential genoprotective activities in normal and adenocarcinoma cell lines
Open accessPublished version of a preprint
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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The central role of DNA damage in the ageing process
Schumacher, B., Pothof, J., Vijg, J., & Hoeijmakers, J. H. J. (2021) · Nature · doi:10.1038/s41586-021-03307-7 · Cited by 907 · see citing works
Flavonoids as Antiobesity Agents: A Review
Rufino, A. T., Costa, V. M., Carvalho, F., & Fernandes, E. (2021) · Medicinal Research Reviews · doi:10.1002/med.21740 · Cited by 174 · see citing works
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- Authors
- 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.
- Affiliations
- University of Ulster (GB)
- James Hutton Institute (GB)
- University of Reading (GB)
- Department of Food Science and Health, IFAPA-Alameda Del Obispo, Córdoba, Spain
- University of Leeds (GB)
- Human Nutrition Unit, Department of Food and Drug, University of Parma, Parma, Italy
- King Saud University (SA)
- University of Canberra (AU)
- Corresponding author
- Gill, Chris I. R.
- ORCID
- Venue
- International Journal of Food Sciences and Nutrition
- Publisher
- Informa UK Limited
- Published
- 2024-09-11
- Volume
- 75
- Issue
- 7
- Pages
- 673-686
- ISSN
- 0963-7486 (ISSN-L)
- 1465-3478
- OpenAlex
- W4402499537
- Cited by
- 0
- References
- 2
- FWCI
- 0.00
- Type
- journal article
- Language
- en
- Open access
- hybrid
- dx.doi.org
- Licence
- Locations
- International Journal of Food Sciences and Nutrition (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- CentAUR (University of Reading) (acceptedVersion)
- Ulster University Research Portal (Ulster University) (submittedVersion, cc-by-nc-nd)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
- Health Sciences › Medicine › Biochemistry › Phytochemicals and Antioxidant Activities
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Keywords
- colonic microbiota, Nrf2/ARE pathway, oxidative DNA damage, genoprotective activity, colon adenocarcinoma, polyphenols, antioxidant response, DNA repair, aging and cancer risk, HT-29 cells
- MeSH terms
- Gastrointestinal Microbiome, Adenocarcinoma, Colon, Colonic Neoplasms, DNA Damage, DNA Repair, Humans, Hydrogen Peroxide, Phenols, Oxidative Stress, HT29 Cells, Cell Line, Tumor, NF-E2-Related Factor 2
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