ArticleScientific reports2015
Nobiletin enhances the efficacy of chemotherapeutic agents in ABCB1 overexpression cancer cells.
Article in Scientific reports, 2015. 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, 87 citations in OpenAlex.
- Time matters: circadian genetics and the molecular logic of human health and disease.Nature reviews. Genetics · 2026Review
- Berberine and its structural diversity: structure-activity relationships, molecular mechanisms, and drug discovery opportunities.Molecular biology reports · 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 Ameliorates Doxorubicin-Induced Nephrotoxicity by Targeting Oxidative Stress, Inflammatory, and Apoptotic Pathways: CombinedACS omega · 2026Article
- Exploring the Therapeutic Potential of Nobiletin in Nonsmall Cell Lung Cancer.BioMed research international · 2026Review
- Cytotoxic Effects ofACS omega · 2025Article
- Citrus flavonoids for overcoming breast cancer resistance to methotrexate: identification of potential targets of nobiletin and sinensetin.Discover oncology · 2025Article
- DADS Regulates EMT and Chemotherapy Resistance by Inhibiting ROROncology research · 2025Article
- Citrus wastewater as a source of value-added products: Quali-quantitative analysis and in vitro screening on breast cancer cell lines.Archiv der Pharmazie · 2024Article
- Unveiling the Potential of Natural Compounds: A Comprehensive Review on Adipose Thermogenesis Modulation.International journal of molecular sciences · 2024Review
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- The superiority of PMFs on reversing drug resistance of colon cancer and the effect on aerobic glycolysis-ROS-autophagy signaling axis.Oncology research · 2024Article
- Crosstalk and plasticity driving between cancer-associated fibroblasts and tumor microenvironment: significance of breast cancer metastasis.Journal of translational medicine · 2023Review
- Destroying the Shield of Cancer Stem Cells: Natural Compounds as Promising Players in Cancer Therapy.Journal of clinical medicine · 2022Review
- Review
- Network Analysis of the Herb-Drug Interactions of Citrus Herbs Inspired by the "Grapefruit Juice Effect".ACS omega · 2022Article
- Novel treatment for refractory rheumatoid arthritis with total glucosides of paeony and nobiletin codelivered in a self-nanoemulsifying drug delivery system.Acta pharmacologica Sinica · 2022Article
- Nobiletin as an inducer of programmed cell death in cancer: a review.Apoptosis : an international journal on programmed cell death · 2022Review
- ROR activation by Nobiletin enhances antitumor efficacy via suppression of IκB/NF-κB signaling in triple-negative breast cancer.Cell death & disease · 2022Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Multidrug resistance (MDR) is the major obstacle to the successful chemotherapy treatment of many cancers. Here we found that nobiletin, a citrus methoxyflavone, significantly sensitized ABCB1 overexpressing cells A2780/T and A549/T to chemotherapeutic agents such as paclitaxel (a 433-fold reversal of MDR to PTX at 9 μM), doxorubicin (DOX), docetaxel and dounorubicin. Nobiletin profoundly inhibited ABCB1 transporter activity since it significantly increased the intracellular accumulation of DOX and Flutax-2 in A2780/T cells and decreased the efflux of ABCB1 substrates in Caco2 cells without altering the mRNA and protein expression of ABCB1. Moreover, nobiletin stimulated ATPase activity and inhibited verapamil-stimulated ATPase activity in a concentration-dependent manner, indicating a direct interaction with the transporter. Consistent with these findings, molecular docking analysis also identified favorable binding of nobiletin with the transmemberane region site 1 of homology modeled human ABCB1 transporter. Moreover, the Nrf2 protein expression and phosphorylation levels of AKT/ERK were suppressed by co-treated with nobiletin and PTX at the reversal concentrations, suggesting that inhibition of the AKT/ERK/Nrf2 pathway was associated with the sensitizing effect of nobiletin. These findings encourage further animal and clinical MDR studies with the combination therapy of nobiletin and chemotherapeutic drugs.
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