ArticlePloS one2023
Development of multi-drug resistance to anticancer drugs in HepG2 cells due to MRP2 upregulation on exposure to menthol.
Article in PloS one, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 5 citations in OpenAlex.
- Targeting drug resistant colorectal cancer with apigenin nanoarchitectures.Translational oncology · 2025Review
- Medicinal Plants for Chemotherapy-Induced Nausea and Vomiting: A Systematic Review of Antiemetic, Chemosensitizing, and Immunomodulatory Mechanisms.Therapeutics and clinical risk management · 2025Review
- Anti-inflammatory and analgesic effects of Kaihoujian throat spray, and therapeutic mechanism in acute pharyngitis: involvement of the NF-κB/COX-2 pathway and formula deconstruction strategy.Frontiers in pharmacology · 2025Article
- Modulation of Multidrug Resistance Transporters by Food Components and Dietary Supplements: Implications for Cancer Therapy Efficacy and Safety.Current issues in molecular biology · 2024Review
- Comparative Cytotoxicity of Menthol and Eucalyptol: An In Vitro Study on Human Gingival Fibroblasts.Pharmaceutics · 2024Article
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Authors and funding
6 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundMenthol exerts relaxing, antibacterial, and anti-inflammatory activities, and is marketed as a functional food and therapeutic drug.
aimIn the present study, the effects of menthol on the expression of multidrug resistance associated protein 2 (MRP2) and its association with the cytotoxicity of epirubicin (EPI) and cisplatin (CIS) were examined using HepG2 cells.
methodsThe expression levels of target genes were examined by real-time PCR. The intracellular concentration of incorporated EPI was measured by high-performance liquid chromatography. Cell viability was evaluated by MTT analysis.
resultsThe expression of MRP2 mRNA was increased by exposing HepG2 cells to menthol for 24 hr. Consistent with a previous report suggesting an inverse correlation between MRP2 and Akt behavior, increased expression of MRP2 was also observed on suppression of the Akt function. Intracellular accumulation of EPI was significantly decreased by exposure of HepG2 cells to menthol, and a significant decrease in the intracellular concentration of EPI remaining was observed in HepG2 cells exposed to menthol. The decreased intracellular accumulation of EPI was significantly suppressed by treatment with MK-571, but not verapamil. Both EPI and CIS exerted cytocidal effects on HepG2 cells, but the decrease in cell viability was significantly attenuated by 24-hr menthol pre-exposure.
conclusionThese results demonstrate that menthol causes hepatocellular carcinoma to acquire resistance to anticancer drugs such as EPI and CIS by MRP2 induction.
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