Inhibitory Effects of Polyphenols on P-Glycoprotein-Mediated Transport

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Overexpression of P-glycoprotein (P-gp), a plasma membrane transporter which extrudes chemotherapeutic agents out of cells, has been associated with the multidrug resistance (MDR) of cancer cells. It has been revealed that flavonoids and other polyphenols inhibit P-gp activity. Due to their inhibitory activities of polyphenols on P-gp function and their physiological safety, they are possible candidates for modulators of MDR. To determine suitable candidates, it is important to clarify the structure–activity relationships of their inhibitory activities on P-gp function. Determining the structure–activity relationships is also meaningful because the intake of dietary polyphenols may also alter drug pharmacokinetics and pharmacodynamics via inhibition of P-gp-mediated drug efflux in tissues such as the intestinal epithelium, blood-brain barrier, hepatocytes and renal tubular cells. This is a review of our recent investigations using multidrug-resistant P-gp overexpressing KB-C2 cells.

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