Natural and synthetic compounds in Ovarian Cancer: A focus on NRF2/KEAP1 pathway
Abstract
Among gynecologic malignancies, ovarian cancer is one of the most dangerous, with a high fatality rate and relapse due to the occurrence of chemoresistance. Many researchers demonstrated that oxidative stress is involved in tumor occurrence, development and procession. Nuclear factor erythroid 2-related factor 2 (NRF2) is an important transcription factor playing an important role in protecting against oxidative damage. Increased levels of Reactive Oxygen Species (ROS) activate NRF2 signaling inducing the expression of antioxidant enzymes such as heme oxygenase (HO-1), catalase (CAT), glutathione peroxidase (GPx) and superoxide dismutase (SOD) that protect cells against oxidative stress. However, NRF2 activation in cancer cells is responsible for the development of chemoresistance inactivating drug-mediated oxidative stress that normally leads cancer cells to death. In this review we analyzed the current literature regarding the role of natural and synthetic compounds in modulating NRF2/KEAP1 (Kelch Like ECH Associated Protein 1) pathway in in vitro models of ovarian cancer. In particular, we reported how these compounds can modulate chemotherapy response.
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The importance of Nrf2 in the protection against human diseases is well established, and much research has explored the use of Nrf2 activators in the treatment of disease.
“The importance of Nrf2 in the protection against human diseases is well established and much research has explored the use of Nrf2 activators in the treatment of disease [220,221,222,223].”
From Nrf2 and Oxidative Stress: A General Overview of Mechanisms and Implications in Human Disease (2022) · cites this paper as [223]
Among Nrf2 modulators, natural compounds target and significantly inhibit the Keap1-Nrf2 pathway, most of which are safe (including dietary phytochemicals) and have shown promise against chemoresistant cancer cells.
“Among these Nrf2 modulators, there are natural compounds that target and significantly inhibit the Keap1-Nrf2 pathway, most of which are safe (including dietary phytochemicals) and have shown promise against chemoresistant cancer cells [223,231].”
From Nrf2 and Oxidative Stress: A General Overview of Mechanisms and Implications in Human Disease (2022) · cites this paper as [223]
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Nrf2 and Oxidative Stress: A General Overview of Mechanisms and Implications in Human Disease
Ngo, V., & Duennwald, M. L. (2022) · Antioxidants · doi:10.3390/antiox11122345 · Cited by 1,130 · see citing works
- Authors
- Tossetta, G., & Marzioni, D.
- Affiliations
- Marche Polytechnic University (IT)
- Corresponding author
- Tossetta, Giovanni
- Venue
- Pharmacological Research
- Publisher
- Elsevier BV
- Published
- 2022-09
- Volume
- 183
- Pages
- 106365
- ISSN
- 1043-6618 (ISSN-L)
- OpenAlex
- W4287448625
- Cited by
- 115
- References
- 99
- Citations by year
- 2026: 11 · 2025: 23 · 2024: 34 · 2023: 35 · 2022: 12
- FWCI
- 2.84
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Pharmacological Research (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Università Politecnica delle Marche (Università Politecnica delle Marche) (submittedVersion)
- Funders
- Ministero della Salute (SG-2018-12367994)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Bioactive Compounds and Antitumor Agents
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glutathione Transferases and Polymorphisms
- Keywords
- ovarian cancer, Nrf2/Keap1 pathway, oxidative stress, reactive oxygen species, chemoresistance, natural compounds, synthetic compounds, heme oxygenase-1, antioxidant enzymes, chemotherapy response, transcription factors
- MeSH terms
- Kelch-Like ECH-Associated Protein 1, Female, Humans, Neoplasm Recurrence, Local, Ovarian Neoplasms, Reactive Oxygen Species, Oxidative Stress, NF-E2-Related Factor 2
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