ArticleFrontiers in genetics2022
Nobiletin Induces Ferroptosis in Human Skin Melanoma Cells Through the GSK3β-Mediated Keap1/Nrf2/HO-1 Signalling Pathway.
Article in Frontiers in genetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.
- The dual role of Nrf2 in melanoma: a systematic review.BMC molecular and cell biology · 2023Pooled it
- Bufalin Suppresses Pancreatic Ductal Adenocarcinoma Through ER Stress-Ferroptosis Crosstalk Associated with IPInternational journal of molecular sciences · 2026Article
- 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
- Cell Death Modalities in Therapy of Melanoma.International journal of molecular sciences · 2025Review
- Natural Products for Melanoma Therapy: From Traditional Medicine to Modern Drug Discovery.Plants (Basel, Switzerland) · 2025Review
- Perfluorooctanoic Acid Induces Ferroptosis in Hepatocytes via Oxidative Stress and AKT/GSK3β/β-Catenin Pathway Disruption.ACS omega · 2025Article
- Mechanistic Insights into the Anticancer Potential of Methoxyflavones Analogs: A Review.Molecules (Basel, Switzerland) · 2025Review
- Jianpi Yangzheng Xiaozheng granule induced ferroptosis to suppress gastric cancer progression through reprogramming lipid metabolism via SCD1/Wnt/β-catenin axis.Frontiers in molecular biosciences · 2025Article
- The Circadian Clock Component RORA Increases Immunosurveillance in Melanoma by Inhibiting PD-L1 Expression.Cancer research · 2024Article
- Experimental verification about treatment of Bu-Shen-Yi-Jing-Fang in Alzheimer's disease by the analysis of the feasible signaling pathway of network pharmacology.BMC complementary medicine and therapies · 2024Article
- Beyond Mortality: Exploring the Influence of Plant Phenolics on Modulating Ferroptosis-A Systematic Review.Antioxidants (Basel, Switzerland) · 2024Review
- Article
- Melanoma biology and treatment: a review of novel regulated cell death-based approaches.Cancer cell international · 2024Review
- Novel Insights on Ferroptosis Modulation as Potential Strategy for Cancer Treatment: When Nature Kills.Antioxidants & redox signaling · 2024Review
- Nobiletin Regulates Polyinosinic-polycytidylic Acid-induced Inflammation in Macrophages PartiallyCurrent pharmaceutical design · 2024Article
- Effects of Natural Products on Enzymes Involved in Ferroptosis: Regulation and Implications.Molecules (Basel, Switzerland) · 2023Review
- A review on the research progress of traditional Chinese medicine with anti-cancer effect targeting ferroptosis.Chinese medicine · 2023Review
- Emerging significance and therapeutic targets of ferroptosis: a potential avenue for human kidney diseases.Cell death & disease · 2023Review
- Molecular mechanisms of ferroptosis and its antitumor applications in natural products.Acta biochimica et biophysica Sinica · 2023Review
- Phytochemical Analysis, In Vitro Biological Activities, and Computer-Aided Analysis ofMolecules (Basel, Switzerland) · 2023Article
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Melanoma is an aggressive malignant skin tumour with an increasing global incidence. However, current treatments have limitations owing to the acquired tumour drug resistance. Ferroptosis is a recently discovered form of programmed cell death characterised by iron accumulation and lipid peroxidation and plays a critical role in tumour growth inhibition. Recently, ferroptosis inducers have been regarded as a promising therapeutic strategy to overcome apoptosis resistance in tumour cells. In this study, we reported that nobiletin, a natural product isolated from citrus peel, and exhibited antitumour activity by inducing ferroptosis in melanoma cells. Subsequently, we further explored the potential mechanism of nobiletin-induced ferroptosis, and found that the expression level of glycogen synthase kinase 3β (GSK3β) in the skin tissue of patients with melanoma was significantly reduced compared to that in the skin of normal tissue. Additionally, nobiletin increased GSK3β expression in melanoma cells. Moreover, the level of Kelch-like Ech-associated protein-1 (Keap1) was increased, while the level of nuclear factor erythroid 2-related factor 2 (Nrf2), and haem oxygenase-1 (HO-1) was decreased in nobiletin-treated melanoma cells, suggesting that the antioxidant defence system was downregulated. Furthermore, knockdown of GSK3β significantly reduced nobiletin-induced ferroptosis and upregulated the Keap1/Nrf2/HO-1 signalling pathway, while the opposite was observed in cells overexpressing GSK3β. In addition, molecular docking assay results indicated that nobiletin showed strong binding affinities for GSK3β, Keap1, Nrf2, and HO-1. Taken together, our results demonstrated that nobiletin could induce ferroptosis by regulating the GSK3β-mediated Keap1/Nrf2/HO-1 signalling pathway in human melanoma cells. Hence, nobiletin stands as a promising drug candidate for melanoma treatment with development prospects.
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