ArticleCell death & disease2022
ROR activation by Nobiletin enhances antitumor efficacy via suppression of IκB/NF-κB signaling in triple-negative breast cancer.
Article in Cell death & disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 64 citations in OpenAlex.
- Time matters: circadian genetics and the molecular logic of human health and disease.Nature reviews. Genetics · 2026Review
- Nobiletin in the modified Yiqi Jianpi Decoction enhances the antitumor activity of CD8The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2026Article
- A novel C5-Horticulture research · 2026Article
- Protein-nucleic acid binding site prediction using interpretable Kolmogorov-Arnold networks with hypergraph representation learning.Bioinformatics (Oxford, England) · 2026Article
- Cryptochrome Loss Drives COPD-like Lung Pathology through Disrupted Alveolar Epithelial Proliferation and Immune Homeostasis.bioRxiv : the preprint server for biology · 2026Article
- Dioscin suppresses tumorigenesis and overcomes radioresistance by promoting ubiquitination-mediated degradation of Mcl-1.Cancer gene therapy · 2026Article
- Chromatin Accessibility in Cancer: Biological Functions, Mechanisms, Therapeutic Potential, and Future Directions.MedComm · 2026Review
- Natural compounds naringin and nobiletin synergistically inhibit the PI3K/AKT/mTOR pathway in NSCLC: molecular docking and cytotoxicity studies.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Nobiletin and polydatin synergistically alleviate triple-negative breast cancer liver metastasis via suppressing ECM1a-mediated fatty acid biosynthesis.Acta pharmacologica Sinica · 2026Article
- Inhibition of the RORC/GPX4 mediated ferroptosis regulatory axis suppresses tumor growth and alleviates enzalutamide resistance in prostate cancer.Cellular & molecular biology letters · 2026Article
- Exploring the Therapeutic Potential of Nobiletin in Nonsmall Cell Lung Cancer.BioMed research international · 2026Review
- The Circadian Modulators as Molecular Targets in Cancer-A Review.International journal of molecular sciences · 2025Review
- Identification of New Lupane-Type Triterpenoids as Inverse Agonists of RAR-Related Orphan Receptor Gamma (RORγ).Journal of natural products · 2025Article
- Nobiletin suppresses nasopharyngeal carcinoma by regulating the KEAP1/NRF2/ARE pathway.Acta biochimica et biophysica Sinica · 2025Article
- Nobiletin reduces 5-FU-induced lung injury with antioxidative, anti-inflammatory and anti-apoptotic activities.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Citrus flavonoids for overcoming breast cancer resistance to methotrexate: identification of potential targets of nobiletin and sinensetin.Discover oncology · 2025Article
- The circadian rhythm: A new target of natural products that can protect against diseases of the metabolic system, cardiovascular system, and nervous system.Journal of advanced research · 2025Review
- Long Intergenic Non-Coding RNAs andNon-coding RNA · 2025Review
- Mechanistic Insights into the Anticancer Potential of Methoxyflavones Analogs: A Review.Molecules (Basel, Switzerland) · 2025Review
- HGH1 Promotes Breast Cancer Progression Through the PI3K/AKT/NF-κB Signaling Pathway: Potential Role for Prognosis and Targeted Therapy.Breast cancer (Dove Medical Press) · 2025Article
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
Abstract
Triple-negative breast cancer (TNBC) is a heterogeneous disease characterized by poor response to standard therapies and therefore unfavorable clinical outcomes. Better understanding of TNBC and new therapeutic strategies are urgently needed. ROR nuclear receptors are multifunctional transcription factors with important roles in circadian pathways and other processes including immunity and tumorigenesis. Nobiletin (NOB) is a natural compound known to display anticancer effects, and our previous studies showed that NOB activates RORs to enhance circadian rhythms and promote physiological fitness in mice. Here, we identified several TNBC cell lines being sensitive to NOB, by itself or in combination. Cell and xenograft experiments showed that NOB significantly inhibited TNBC cell proliferation and motility in vitro and in vivo. ROR loss- and gain-of-function studies showed concordant effects of the NOB-ROR axis on MDA-MB-231 cell growth. Mechanistically, we found that NOB activates ROR binding to the ROR response elements (RRE) of the IκBα promoter, and NOB strongly inhibited p65 nuclear translocation. Consistent with transcriptomic analysis indicating cancer and NF-κB signaling as major pathways altered by NOB, p65-inducible expression abolished NOB effects, illustrating a requisite role of NF-κB suppression mediating the anti-TNBC effect of NOB. Finally, in vivo mouse xenograft studies showed that NOB enhanced the antitumor efficacy in mammary fat pad implanted TNBC, as a single agent or in combination with the chemotherapy agent Docetaxel. Together, our study highlights an anti-TNBC mechanism of ROR-NOB via suppression of NF-κB signaling, suggesting novel preventive and chemotherapeutic strategies against this devastating disease.
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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.