ArticleJournal of experimental & clinical cancer research : CR2021
Flavonoids kaempferol and quercetin are nuclear receptor 4A1 (NR4A1, Nur77) ligands and inhibit rhabdomyosarcoma cell and tumor growth.
Article in Journal of experimental & clinical cancer research : CR, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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35 citing papers in PubMed, 51 citations in OpenAlex.
- MerTK Is Regulated by Orphan Nuclear Receptor 4A1 (NR4A1) and NR4A2 in Colon Cancer Cells.Cancers · 2026Article
- Unveiling medication patterns in traditional Chinese medicine for the prevention of colorectal cancer recurrence: from potential combinations to validation of components and targets.Chinese medicine · 2026Article
- Article
- Citrus flavanones (naringenin, hesperidin, and hesperetin) in oral and gastric carcinogenesis: mechanistic insights into oxidative stress, cell death, epigenetic regulation, non-coding RNAs, and tumor microenvironment remodeling.Frontiers in cell and developmental biology · 2026Review
- Network pharmacology and experimental evidence of the anti-colorectal cancer potential of Xian Lian Jie Du formula: quercetin, kaempferol and luteolin jointly inhibit the HIF1A/IL6/TNF oncogenic pathway.Frontiers in oncology · 2026Article
- Orphan nuclear receptor 4A1 (NR4A1) and NR4A2 are endogenous regulators of CD71 and their ligands induce ferroptosis in breast cancer.Cell death & disease · 2025Article
- Comparative Profiling and Chemogenomics Application of Chemical Tools for NR4A Nuclear Receptors.Journal of medicinal chemistry · 2025Article
- Nuclear receptors in metabolic, inflammatory, and oncologic diseases: mechanisms, therapeutic advances, and future directions.European journal of medical research · 2025Review
- Review
- Chrysin: A Comprehensive Review of Its Pharmacological Properties and Therapeutic Potential.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Targeting Lineage-Specific Functions of NR4A1 for Cancer Immunotherapy.International journal of molecular sciences · 2025Review
- Perfluorooctane Sulfonate (PFOS) and Related Compounds Induce Nuclear Receptor 4A1 (NR4A1)-Dependent Carcinogenesis.Chemical research in toxicology · 2025Article
- Article
- Functional Changes Associated With the Subcellular Localization of the Nuclear Receptor NR4A1.Biochemistry research international · 2025Review
- Unlocking the Potential: How Flavonoids Affect Angiogenesis, Oxidative Stress, Inflammation, Proliferation, Invasion, and Alter Receptor Interactions in Endometriosis.Food science & nutrition · 2025Review
- Crippled Hepatocarcinogenesis Inhibition of Quercetin in Glycolysis Pathway with Hepatic Farnesoid X Receptor Deficiency.Current pharmaceutical design · 2025Article
- Semaglutide ameliorates cardiac remodeling in male mice by optimizing energy substrate utilization through the Creb5/NR4a1 axis.Nature communications · 2024Article
- Nur77-IRF1 axis inhibits esophageal squamous cell carcinoma growth and improves anti-PD-1 treatment efficacy.Cell death discovery · 2024Article
- Natural products and synthetic analogs as selective orphan nuclear receptor 4A (NR4A) modulators.Histology and histopathology · 2024Review
- Kaempferol enhances intestinal repair and inhibits the hyperproliferation of aging intestinal stem cells inFrontiers in cell and developmental biology · 2024Article
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundFlavonoids exhibit both chemopreventive and chemotherapeutic activity for multiple tumor types, however, their mechanisms of action are not well defined. Based on some of their functional and gene modifying activities as anticancer agents, we hypothesized that kaempferol and quercetin were nuclear receptor 4A1 (NR4A1, Nur77) ligands and confirmed that both compounds directly bound NR4A1 with K
methodsThe activities of kaempferol and quercetin were determined in direct binding to NR4A1 protein and in NR4A1-dependent transactivation assays in Rh30 and Rh41 rhabdomyosarcoma (RMS) cells. Flavonoid-dependent effects as inhibitors of cell growth, survival and invasion were determined in XTT and Boyden chamber assays respectively and changes in protein levels were determined by western blots. Tumor growth inhibition studies were carried out in athymic nude mice bearing Rh30 cells as xenografts.
resultsKaempferol and quercetin bind NR4A1 protein and inhibit NR4A1-dependent transactivation in RMS cells. NR4A1 also regulates RMS cell growth, survival, mTOR signaling and invasion. The pro-oncogenic PAX3-FOXO1 and G9a genes are also regulated by NR4A1 and, these pathways and genes are all inhibited by kaempferol and quercetin. Moreover, at a dose of 50 mg/kg/d kaempferol and quercetin inhibited tumor growth in an athymic nude mouse xenograft model bearing Rh30 cells.
conclusionThese results demonstrate the clinical potential for repurposing kaempferol and quercetin for clinical applications as precision medicine for treating RMS patients that express NR4A1 in order to increase the efficacy and decrease dosages of currently used cytotoxic drugs.
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