title: Inhibition of the multidrug resistance P-glycoprotein activity by green tea polyphenols.
abstract: Many beneficial proprieties have been associated with polyphenols from green tea, such as chemopreventive, anticarcinogenic, antiatherogenic and antioxidant actions. In this study, we investigated the effects of green tea polyphenols (GTPs) and their principal catechins on the function of P-glycoprotein (P-gp), which is involved in the multidrug resistance phenotype of cancer cells. GTPs (30 microg/ml) inhibit the photolabeling of P-gp by 75% and increase the accumulation of rhodamine-123 (R-123) 3-fold in the multidrug-resistant cell line CH(R)C5, indicating that GTPs interact with P-gp and inhibit its transport activity. Moreover, the modulation of P-gp transport by GTPs was a reversible process. Among the catechins present in GTPs, EGCG, ECG and CG are responsible for inhibiting P-gp. In addition, EGCG potentiates the cytotoxicity of vinblastine (VBL) in CH(R)C5 cells. The inhibitory effect of EGCG on P-gp was also observed in human Caco-2 cells, which form an intestinal epithelial-like monolayer. Our results indicate that, in addition to their anti-cancer properties, GTPs and more particularly EGCG inhibit the binding and efflux of drugs by P-gp. Thus, GTPs or EGCG might be potential agents for modulating the bioavailability of P-gp substrates at the intestine and the multidrug resistance phenotype associated with expression of this transporter in cancer cells.
authors.affiliation: Laboratoire de Médecine Moléculaire, Centre de Cancérologie Charles Bruneau, Université du Québec à Montréal, Canada.
authors.forename: Julie
authors.initials: J
authors.lastname: Jodoin
authors.forename: Michel
authors.initials: M
authors.lastname: Demeule
authors.forename: Richard
authors.initials: R
authors.lastname: Beliveau
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis / Q000037:antagonists & inhibitors*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D016466:CHO Cells; D018938:Caco-2 Cells; D028241:Camellia sinensis; D002392:Catechin / Q000031:analogs & derivatives / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D006224:Cricetinae; D018432:Drug Resistance, Multiple; D005419:Flavonoids; D006801:Humans; D010636:Phenols / Q000494:pharmacology*; D011108:Polymers / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D020112:Rhodamine 123 / Q000494:pharmacology; D014747:Vinblastine / Q000494:pharmacology
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D005419:Flavonoids; D010636:Phenols; D011108:Polymers; D020112:Rhodamine 123; D014747:Vinblastine; D002392:Catechin; C045651:epigallocatechin gallate