ArticlePhytomedicine : international journal of phytotherapy and phytopharmacology2019
Tenulin and isotenulin inhibit P-glycoprotein function and overcome multidrug resistance in cancer cells.
Article in Phytomedicine : international journal of phytotherapy and phytopharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 38 citations in OpenAlex.
- Nanomedicine strategies for overcoming multidrug resistance in breast cancer: recent advances and future perspectives.Journal of the Egyptian National Cancer Institute · 2026Review
- Re-sensitization of cancer multidrug resistance through P-gp, MRP1 and BCRP modulation: advances in terpenoids based cancer therapy.Discover oncology · 2025Review
- Targeting drug resistant colorectal cancer with apigenin nanoarchitectures.Translational oncology · 2025Review
- Identification of osteoarthritis-associated chondrocyte subpopulations and key gene-regulating drugs based on multi-omics analysis.Scientific reports · 2025Article
- Current Progress of Hederagenin and Its Derivatives for Disease Therapy (2017-Present).Molecules (Basel, Switzerland) · 2025Review
- Influence of Nanomedicine as a Smart Weapon for Multidrug Resistance in Cancer Therapy.Current pharmaceutical biotechnology · 2025Review
- Role of natural P-gp inhibitor in the effective delivery for chemotherapeutic agents.Journal of cancer research and clinical oncology · 2023Review
- Phytol and Heptacosane Are Possible Tools to Overcome Multidrug Resistance in an In Vitro Model of Acute Myeloid Leukemia.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Targeting Drug Chemo-Resistance in Cancer Using Natural Products.Biomedicines · 2021Review
- Chemoresistance and Metastasis in Breast Cancer Molecular Mechanisms and Novel Clinical Strategies.Frontiers in oncology · 2021Review
- A New Chalcone Derivative C49 Reverses Doxorubicin Resistance in MCF-7/DOX Cells by Inhibiting P-Glycoprotein Expression.Frontiers in pharmacology · 2021Article
- Antimicrobial Peptide Reverses ABCB1-Mediated Chemotherapeutic Drug Resistance.Frontiers in pharmacology · 2020Article
- CTAB Enhances Chemo-Sensitivity Through Activation of AMPK Signaling Cascades in Breast Cancer.Frontiers in pharmacology · 2019Article
- Anemoside B4 exerts anti-cancer effect by inducing apoptosis and autophagy through inhibiton of PI3K/Akt/mTOR pathway in hepatocellular carcinoma.American journal of translational research · 2019Article
- Taxifolin Resensitizes Multidrug Resistance Cancer Cells via Uncompetitive Inhibition of P-Glycoprotein Function.Molecules (Basel, Switzerland) · 2018Article
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundMultidrug resistance (MDR) in cancer is one of the main obstacles in treatment with chemotherapy. Drug efflux through P-glycoprotein is the major mechanism involved in MDR. A potential strategy to provide the best possible clinical outcomes is to develop P-glycoprotein (P-gp) inhibitors from natural products. PURPOSE: The present study investigated the effects of the natural sesquiterpene lactone tenulin and its derivative isotenulin on human P-gp; the mechanisms of kinetic interactions were also explored.
methodsThe human P-gp (ABCB1/Flp-In™-293) stable expression cells were established by using the Flp-In™ system. The effects of tenulin and isotenulin on cell viability were evaluated by SRB assays in established cell lines, sensitive cancer cell line (HeLaS3), and resistant cancer cell line (KB-vin). The transporter inhibition ability was evaluated by calcein-AM uptake assays. The P-gp inhibition kinetics of tenulin and isotenulin were evaluated by rhodamine123 and doxorubicin efflux assays. The ATPase activity was evaluated with the Pgp-Glo™ Assay System.
resultsTenulin and isotenulin significantly inhibited the P-gp efflux function by stimulating P-gp ATPase activity. Tenulin and isotenulin interacted with the effluxes of rhodamine 123 and doxorubicin through a competitive and noncompetitive mechanism, respectively. The combinations of tenulin and isotenulin with chemotherapeutic drugs significantly resensitized MDR cancer cells.
conclusionThese results suggested that tenulin and isotenulin are potential candidates to be developed for synergistic treatment of MDR cancers.
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