Involvement of NRF2 in Breast Cancer and Possible Therapeutical Role of Polyphenols and Melatonin
Open accessAbstract
Oxidative stress is defined as a disturbance in the prooxidant/antioxidant balance in favor of the former and a loss of control over redox signaling processes, leading to potential biomolecular damage. It is involved in the etiology of many diseases, varying from diabetes to neurodegenerative diseases and cancer. Nuclear factor erythroid 2-related factor 2 (NRF2) is a transcription factor and reported as one of the most important oxidative stress regulators. Due to its regulatory role in the expression of numerous cytoprotective genes involved in the antioxidant and anti-inflammatory responses, the modulation of NRF2 seems to be a promising approach in the prevention and treatment of cancer. Breast cancer is the prevalent type of tumor in women and is the leading cause of death among female cancers. Oxidative stress-related mechanisms are known to be involved in breast cancer, and therefore, NRF2 is considered to be beneficial in its prevention. However, its overactivation may lead to a negative clinical impact on breast cancer therapy by causing chemoresistance. Some known “oxidative stress modulators”, such as melatonin and polyphenols, are suggested to play an important role in the prevention and treatment of cancer, where the activation of NRF2 is reported as a possible underlying mechanism. In the present review, the potential involvement of oxidative stress and NRF2 in breast cancer will be reviewed, and the role of the NRF2 modulators—namely, polyphenols and melatonin—in the treatment of breast cancer will be discussed.
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There are initial indications that the antioxidant and anti-inflammatory actions of melatonin may work together with select polyphenols (e.g., resveratrol, epigallocatechin 3-gallate) for therapeutic indications.
“There are initial indications that the antioxidant and anti-inflammatory actions of melatonin may work together with select polyphenols (e.g., resveratrol, epigallocatechin 3-gallate) for therapeutic indications [48,49,50,51,52,53,54].”
From Is Melatonin the “Next Vitamin D”?: A Review of Emerging Science, Clinical Uses, Safety, and Dietary Supplements (2022) · cites this paper as [48]
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1 of the 92 references couldn’t be matched to a known paper.
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Nrf2 Modulation in Breast Cancer
Ghareghomi, S., Habibi-Rezaei, M., Arese, M., Saso, L., & Moosavi‐Movahedi, A. A. (2022) · Biomedicines · doi:10.3390/biomedicines10102668 · Cited by 97 · see citing works
Self-citationRole of Nrf2 Signaling Cascade in Breast Cancer: Strategies and Treatment
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Exploring the Mechanical Perspective of a New Anti-Tumor Agent: Melatonin
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Brain Neurotrophins and Plant Polyphenols: A Powerful Connection
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Mitigation of Cardiovascular Disease and Toxicity through NRF2 Signalling
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Alkaloids as Natural NRF2 Inhibitors: Chemoprevention and Cytotoxic Action in Cancer
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Dual role of Nrf2 in cancer: molecular mechanisms, cellular functions and therapeutic interventions
Poornashree, M., Kumar, H., AJMEER, R., Jain, R., & Jain, V. K. (2022) · Molecular Biology Reports · doi:10.1007/s11033-022-08126-1 · Cited by 28 · see citing works
González‐Bosch, C., Zunszain, P. A., & Mann, G. E. (2023) · Pathogens · doi:10.3390/pathogens12030486 · Cited by 27 · see citing works
NFR2/ABC transporter axis in drug resistance of breast cancer cells
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Nabih, H. K., Hamed, A. R., & Yahya, S. M. M. (2023) · Scientific Reports · doi:10.1038/s41598-023-31443-9 · Cited by 16 · see citing works
NRF2 Modulators of Plant Origin and Their Ability to Overcome Multidrug Resistance in Cancers
Wadowski, P., Juszczak, M., & Woźniak, K. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252111500 · Cited by 14 · see citing works
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Prognostic Worth of Nrf2/BACH1/HO-1 Protein Expression in the Development of Breast Cancer
Barnes, P., Agbo, E., Wang, J., Amoani, B., Opoku, Y. K., Okyere, P., & Saahene, R. O. (2023) · Medical Principles and Practice · doi:10.1159/000534534 · Cited by 6 · see citing works
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Redox Active Molecules in Cancer Treatments
Stepanić, V., & Kučerová-Chlupáčová, M. (2023) · Molecules · doi:10.3390/molecules28031485 · Cited by 3 · see citing works
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A computational reference for human genomics analysis in (poly)phenol research
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Exploration of the scutellarin effect on breast cancer based on network pharmacology
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Nrf2 Modulators and the Prospects of Indigenous Medicinal Plants
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A relação inversamente proporcional entre melatonina e estrogênio no câncer de mama
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Melatonin and Cancer: New Insights
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The Dual Role of NRF2 Transcription Factor in Female Cancer
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NRF2‐Regulated Ferroptosis in Breast Cancer: Mechanisms, Resistance, and Therapeutic Opportunities
Al-Hawary, S. I. S., Vasudevan, A., Rodrigues, S. R., Turakulov, R., R.Baig, M., Nematov, O., Tailor, N. K., Singhal, D., & Nayak, P. P. (2026) · Asia-Pacific Journal of Clinical Oncology · doi:10.1111/ajco.70195
- Authors
- Tascioglu Aliyev, A., Panieri, E., Stepanić, V., Gurer-Orhan, H., & Saso, L.
- Affiliations
- Department of Toxicology, Faculty of Pharmacy, Ege University, 35040 Izmir, Turkey
- Sapienza University of Rome (IT)
- Ruđer Bošković Institute (HR)
- Venue
- Molecules
- Publisher
- MDPI AG
- Published
- 2021-03-25
- Volume
- 26
- Issue
- 7
- Pages
- 1853
- ISSN
- 1420-3049 (ISSN-L)
- PMC
- PMC8038098
- OpenAlex
- W3141973448
- Cited by
- 50
- References
- 92
- Citations by year
- 2026: 6 · 2025: 6 · 2024: 10 · 2023: 14 · 2022: 12 · 2021: 2
- FWCI
- 1.00
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Molecules (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Institutional Repository of the Ruđer Bošković Institute (Ruđer Bošković Institute) (submittedVersion, cc-by)
- Funders
- Ege Üniversitesi
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Bioactive Compounds and Antitumor Agents
- Keywords
- Nrf2, breast cancer, oxidative stress, polyphenols, melatonin, chemoresistance, antioxidant defense, redox signaling, cancer prevention, cancer therapy
- MeSH terms
- Breast Neoplasms, Female, Humans, Melatonin, Neoplasm Proteins, Oxidative Stress, Drug Resistance, Neoplasm, NF-E2-Related Factor 2, Polyphenols
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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