ArticleBritish journal of pharmacology2012
Cellular pharmacokinetic mechanisms of adriamycin resistance and its modulation by 20(S)-ginsenoside Rh2 in MCF-7/Adr cells.
Article in British journal of pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 88 citations in OpenAlex.
- Ginsenosides Rh2 and Rg3 in first-line combination therapy: Prospects for rapid clinical translation in drug-resistant triple-negative breast cancer.Journal of ginseng research · 2026Review
- Molecular Evidence of the Bio-activities of Traditional Home Medicine Ingredients.Current topics in medicinal chemistry · 2025Review
- The ways for ginsenoside Rh2 to fight against cancer: the molecular evidencesJournal of ginseng research · 2023Review
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- Molecular and cellular paradigms of multidrug resistance in cancer.Cancer reports (Hoboken, N.J.) · 2022Review
- New opportunities and challenges of natural products research: When target identification meets single-cell multiomics.Acta pharmaceutica Sinica. B · 2022Review
- Probable Mechanisms of Doxorubicin Antitumor Activity Enhancement by Ginsenoside Rh2.Molecules (Basel, Switzerland) · 2022Article
- Pharmacodynamics and Cellular Uptake of Peimine and Peiminine in Inflammatory Model Non-Small-Cell Lung Cancer Epithelial Cells (A549).Evidence-based complementary and alternative medicine : eCAM · 2022Article
- Ginsenoside 20(S)-Rh2 promotes cellular pharmacokinetics and intracellular antibacterial activity of levofloxacin against Staphylococcus aureus through drug efflux inhibition and subcellular stabilization.Acta pharmacologica Sinica · 2021Article
- Ginsenosides emerging as both bifunctional drugs and nanocarriers for enhanced antitumor therapies.Journal of nanobiotechnology · 2021Review
- Article
- Emerging Significance of Ginsenosides as Potentially Reversal Agents of Chemoresistance in Cancer Therapy.Frontiers in pharmacology · 2021Review
- Metabolic Pathways and Targets in Chondrosarcoma.Frontiers in oncology · 2021Review
- Shenmai injection suppresses multidrug resistance in MCF-7/ADR cells through the MAPK/NF-κB signalling pathway.Pharmaceutical biology · 2020Article
- Traditional Herbal Medicine Mediated Regulations during Head and Neck Carcinogenesis.Biomolecules · 2020Review
- Mechanisms and pharmacokinetic/pharmacodynamic profiles underlying the low nephrotoxicity and ototoxicity of etimicin.Acta pharmacologica Sinica · 2020Article
- Article
- Article
- Ginsenoside Rg5 overcomes chemotherapeutic multidrug resistance mediated by ABCB1 transporter:Journal of ginseng research · 2020Article
- Naturally occurring anti-cancer compounds: shining from Chinese herbal medicine.Chinese medicine · 2019Review
Corrections and comments
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Authors and funding
13 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeIntracellular pharmacokinetics of anticancer drugs in multi-drug resistance (MDR) cancer cells is hugely important in the evaluation and improvement of drug efficacy. By using adriamycin as a probe drug in MDR cancer cells, we developed a cellular pharmacokinetic-pharmacodynamic (PK-PD) model to reveal the correlation between cellular pharmacokinetic properties and drug resistance. In addition, the ability of 20(S)-ginsenoside Rh2 (20(S)-Rh2) to reverse MDR was further investigated. EXPERIMENTAL APPROACH: The cellular pharmacokinetics of adriamycin were analysed visually and quantitatively in human breast cancer cells MCF-7 and in adriamycin-resistant MCF-7 (MCF-7/Adr) cells. Mitochondria membrane potential was assayed to evaluate the apoptotic effect of adriamycin. Subsequently, a PK-PD model was developed via MATLAB. KEY
resultsVisual and quantitative data of the dynamic subcellular distribution of adriamycin revealed that it accumulated in cells, especially nuclei, to a lesser and slower extent in MCF-7/Adr than in MCF-7 cells. 20(S)-Rh2 increased the rate and amount of adriamycin entering cellular/subcellular compartments in MCF-7/Adr cells through inhibition of P-glycoprotein (P-gp) activity, in turn augmenting adriamycin-induced apoptosis. The integrated PK-PD model mathematically revealed the pharmacokinetic mechanisms of adriamycin resistance in MCF-7/Adr cells and its reversal by 20(S)-Rh2. CONCLUSIONS AND IMPLICATIONS: P-gp, which is overexpressed and functionally active at cellular/subcellular membranes, influences the cellular pharmacokinetic and pharmacological properties of adriamycin in MCF-7/Adr cells. Inhibition of P-gp activity represents a key mechanism by which 20(S)-Rh2 attenuates adriamycin resistance. Even more importantly, our findings provide a new strategy to explore the in-depth mechanisms of MDR and evaluate the efficacy of MDR modulators.
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