ArticleBreast cancer research and treatment2010
Inhibition of estrogen signaling activates the NRF2 pathway in breast cancer.
Article in Breast cancer research and treatment, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 88 citations in OpenAlex.
- Estrogen receptor and PI3K/Akt signaling pathway involvement in S-(-)equol-induced activation of Nrf2/ARE in endothelial cells.PloS one · 2013Trial
- Mitochondrial Redox Vulnerabilities in Triple-Negative Breast Cancer: Integrative Perspectives and Emerging Therapeutic Strategies.Metabolites · 2026Review
- Estrogen receptors and the NRF2 pathway: bridging hormonal regulation and stress response in the gut.Frontiers in endocrinology · 2026Review
- Effect of Estrogen on Sirt1 Signaling in Human Macrophages.International journal of molecular sciences · 2025Article
- Review on Natural Agents as Aromatase Inhibitors: Management of Breast Cancer.Combinatorial chemistry & high throughput screening · 2024Review
- NQO1/CPT1A promotes the progression of pancreatic adenocarcinoma via fatty acid oxidation.Acta biochimica et biophysica Sinica · 2023Article
- Inhibitors of Keap1-Nrf2 protein-protein interaction reduce estrogen responsive gene expression and oxidative stress in estrogen receptor-positive breast cancer.Toxicology and applied pharmacology · 2023Article
- The ERα-NRF2 signalling axis promotes bicalutamide resistance in prostate cancer.Cell communication and signaling : CCS · 2022Article
- Natural Small Molecules in Breast Cancer Treatment: Understandings from a Therapeutic Viewpoint.Molecules (Basel, Switzerland) · 2022Review
- Herbal Ingredients in the Prevention of Breast Cancer: Comprehensive Review of Potential Molecular Targets and Role of Natural Products.Oxidative medicine and cellular longevity · 2022Review
- Polymorphic estrogen receptor binding site causes Cd2-dependent sex bias in the susceptibility to autoimmune diseases.Nature communications · 2021Article
- Effects of shikonin on the development of ovarian follicles and female germline stem cells.The Journal of international medical research · 2021Article
- Sirtuins-The New Important Players in Women's Gynecological Health.Antioxidants (Basel, Switzerland) · 2021Review
- Shikonin inhibits migration and invasion of triple-negative breast cancer cells by suppressing epithelial-mesenchymal transition via miR-17-5p/PTEN/Akt pathway.Journal of Cancer · 2021Article
- A Splice Variant of NCOR2, BQ323636.1, Confers Chemoresistance in Breast Cancer by Altering the Activity of NRF2.Cancers · 2020Article
- Pharmacological Applications of Nrf2 Inhibitors as Potential Antineoplastic Drugs.International journal of molecular sciences · 2019Review
- Dissecting the prevention of estrogen-dependent breast carcinogenesis through Nrf2-dependent and independent mechanisms.OncoTargets and therapy · 2019Review
- Sexual Dimorphism in Response to an NRF2 Inducer in a Model for Pachyonychia Congenita.The Journal of investigative dermatology · 2018Article
- Anticancer Efficacy of Targeted Shikonin Liposomes Modified with RGD in Breast Cancer Cells.Molecules (Basel, Switzerland) · 2018Article
- SIRT1 and Estrogen Signaling Cooperation for Breast Cancer Onset and Progression.Frontiers in endocrinology · 2018Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Exposure to higher levels of estrogen produces genotoxic metabolites that can stimulate mammary tumorigenesis. Induction of NF-E2-related factor 2 (NRF2)-dependent detoxifying enzymes (e.g., NAD(P)H-quinone oxidoreductase 1 (NQO1)) is considered an important mechanism of protection against estrogen-associated carcinogenesis because they would facilitate removal of toxic estrogens. Here, we studied the impact of estrogen-receptor (ER) signaling on NRF2-dependent gene transcription. In luciferase assay experiments using the 5-flanking region of the human NQO1 gene promoter, we observe that ERα ligand-binding domain (LBD) is required for estrogen inhibition of NQO1 promoter activity in estrogen-dependent breast cancer cells. Chromatin immunoprecipitation (ChIP) assay shows that estrogen recruits ERα and a class III histone deacetylase SIRT1 at the NQO1 promoter, leading to inhibition of NQO1 transcription. Inhibition of ERα expression by the antiestrogen shikonin reverses the inhibitory effect of estrogen on NQO1 expression. As a consequence, a chemoprevention study was undertaken to monitor the impact of shikonin on DNA lesions and tumor growth. Treatment of MCF-7 breast cancer cells with shikonin inhibits estrogen-induced 8-hydroxy-2-deoxyguanosine (8-OHdG), a marker of DNA damage. NQO1 deficiency promotes estrogen-dependent tumor formation, and shikonin inhibits estrogen-dependent tumor growth in an NQO1-dependent manner in MCF-7 xenografts. These results suggest that estrogen-receptor signaling pathway has an inhibitory effect on NRF2-dependent enzymes. Moreover, shikonin reverses the inhibitory effects of estrogen on this pathway and may contribute to breast cancer prevention.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.