Genistein and Procyanidin B2 Reduce Carcinogen-Induced Reactive Oxygen Species and DNA Damage through the Activation of Nrf2/ARE Cell Signaling in Bronchial Epithelial Cells In Vitro
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Cancer is one of the leading causes of death worldwide. Chemotherapy and radiation therapy are currently providing the basis for cancer therapies, although both are associated with significant side effects. Thus, cancer prevention through dietary modifications has been receiving growing interest. The potential of selected flavonoids in reducing carcinogen-induced reactive oxygen species (ROS) and DNA damage through the activation of nuclear factor erythroid 2 p45 (NF-E2)-related factor (Nrf2)/antioxidant response element (ARE) pathway was studied in vitro. Dose-dependent effects of pre-incubated flavonoids on pro-carcinogen 4-[(acetoxymethyl)nitrosamino]-1-(3-pyridyl)-1-butanone (NNKAc)-induced ROS and DNA damage in human bronchial epithelial cells were studied in comparison to non-flavonoids. The most effective flavonoids were assessed for the activation of Nrf2/ARE pathway. Genistein, procyanidin B2 (PCB2), and quercetin significantly suppressed the NNKAc-induced ROS and DNA damage. Quercetin significantly upregulated the phosphorylated protein kinase B/Akt. PCB2 significantly upregulated the activation of Nrf2 and Akt through phosphorylation. Genistein and PCB2 significantly upregulated the phospho-Nrf2 nuclear translocation and catalase activity. In summary, genistein and PCB2 reduced the NNKAc-induced ROS and DNA damage through the activation of Nrf2. Further studies are required to understand the role of dietary flavonoids on the regulation of the Nrf2/ARE pathway in relation to carcinogenesis.
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Genistein reduces NNKAc-induced ROS and DNA damage through activation of Nrf2.
“genistein has also been shown to reduce NNKAc-induced ROS and DNA damage through the activation of Nrf2”
From Drug repurposing for cancer therapy (2024) · cites this paper as [175]
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Natural Compounds Used in Targeting Cellular Organelles for Drug Delivery
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- Authors
- Suraweera, T. L., Merlin, J. P. J., Dellaire, G., Xu, Z., & Rupasinghe, H. P. V.
- Affiliations
- Dalhousie University (CA)
- Corresponding author
- Rupasinghe, H. P. Vasantha
- Venue
- International Journal of Molecular Sciences
- Publisher
- MDPI AG
- Published
- 2023-02-12
- Volume
- 24
- Issue
- 4
- Pages
- 3676
- ISSN
- 1422-0067 (ISSN-L)
- PMC
- PMC9961944
- OpenAlex
- W4320493371
- Cited by
- 35
- References
- 75
- Citations by year
- 2026: 8 · 2025: 10 · 2024: 11 · 2023: 6
- FWCI
- 3.11
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- International Journal of Molecular Sciences (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Discovery Grant of the Natural Sciences and Engineering Research Council (NSERC) of Canada (RGPIN2016 05369)
- Beatrice Hunter Cancer Research Institute (RGPIN2016 05369)
- CIBC (RGPIN2016 05369)
- 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 › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Bioactive Compounds and Antitumor Agents
- Keywords
- genistein, procyanidin B2, quercetin, Nrf2/ARE pathway, reactive oxygen species, DNA damage, bronchial epithelial cells, flavonoids, Akt signaling, catalase, Nrf2 nuclear translocation, chemoprevention, dietary flavonoids
- MeSH terms
- Carcinogens, Catechin, DNA Damage, Epithelial Cells, Flavonoids, Humans, Quercetin, Signal Transduction, Reactive Oxygen Species, Oxidative Stress, Genistein, Proanthocyanidins, Biflavonoids, Proto-Oncogene Proteins c-akt, NF-E2-Related Factor 2, Antioxidant Response Elements
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