ABCB1 (MDR1/P-glycoprotein), the best characterized multidrug transporter belonging to the ABC transporter superfamily, is nowadays acknowledged to have a major impact on drug resistance to chemotherapy and drug bioavailability and disposition. A number of natural compounds, dietary phytochemicals and herbal remedies have the ability to modulate P-glycoprotein function and /or expression and therefore the potentiality to cause food-drug, or herb-drug interactions. The elucidation of these interactions may be important not only to predict possible undesirable effects deriving from the concomitant intake of herbal constituents and conventional drugs, but also for further studies of positive uses of these interactions as a way to increase the bioavailability of drugs that are P-gp substrates. In particular, the study of P-gp inhibition by herbal constituents may provide an approach for the identification of lead compounds for the design of news chemosensitizers to reverse multidrug resistance in tumor cells. This review describes our recent investigations on the potential herb-drug interactions involving P-glycoprotein, using as a model the HK-2 cells, an immortalized line of proximal tubule cell derived from human normal kidney.
Kidney proximal human tubule HK-2 cell line as a tool for the investigation of P-glycoprotein modulation by natural compounds
CHIELI, ELISABETTA;ROMITI, NADIA
2008-01-01
Abstract
ABCB1 (MDR1/P-glycoprotein), the best characterized multidrug transporter belonging to the ABC transporter superfamily, is nowadays acknowledged to have a major impact on drug resistance to chemotherapy and drug bioavailability and disposition. A number of natural compounds, dietary phytochemicals and herbal remedies have the ability to modulate P-glycoprotein function and /or expression and therefore the potentiality to cause food-drug, or herb-drug interactions. The elucidation of these interactions may be important not only to predict possible undesirable effects deriving from the concomitant intake of herbal constituents and conventional drugs, but also for further studies of positive uses of these interactions as a way to increase the bioavailability of drugs that are P-gp substrates. In particular, the study of P-gp inhibition by herbal constituents may provide an approach for the identification of lead compounds for the design of news chemosensitizers to reverse multidrug resistance in tumor cells. This review describes our recent investigations on the potential herb-drug interactions involving P-glycoprotein, using as a model the HK-2 cells, an immortalized line of proximal tubule cell derived from human normal kidney.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
