Inhibition of P-glycoprotein and multidrug resistance protein 1 by dietary phytochemicals

Cancer Chemotherapy and Pharmacology
Tomohiro NabekuraShuji Kitagawa

Abstract

For the development of a safe and effective dual inhibitor of anticancer drug efflux transporters P-glycoprotein and multidrug resistance protein 1 (MRP1) to conquer multidrug resistance, we investigated the effects of dietary phytochemicals on the functions of P-glycoprotein and MRP1. The effects of dietary phytochemicals on the functions of P-glycoprotein and MRP1 were investigated using P-glycoprotein-overexpressing human carcinoma KB-C2 cells and human MRP1 gene-transfected KB/MRP cells. The effects of natural compounds found in dietary supplements, herbs, and foods such as sesame, ginkgo, soybean, and licorice were evaluated. The accumulation of daunorubicin, a fluorescent substrate of P-glycoprotein, increased in the presence of sesamin, ginkgolic acid, matairesinol, glycyrrhetinic acid, glabridin, and phyllodulcin in KB-C2 cells. Glycyrrhetinic acid and matairesinol also increased the accumulation of calcein, a fluorescent substrate of MRP1, in KB/MRP cells. KB-C2 and KB/MRP cells were sensitized to anticancer drugs by glycyrrhetinic acid, showing that glycyrrhetinic acid reverses multidrug resistance. The verapamil-stimulated P-glycoprotein ATPase activity was inhibited by glycyrrhetinic acid. Glycyrrhetinic acid stimul...Continue Reading

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Citations

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