title: Inhibitory activity of a green tea extract and some of its constituents on multidrug resistance-associated protein 2 functionality.
abstract: Green tea extracts (GTE) might modulate ABC transporter gene expression or function. This may be relevant in the treatment of cancer or in influencing intestinal drug permeability. To gain more insight on the influence of a GTE on secretory transport proteins we investigated the influence of GTE and several green tea components on the mRNA expression level of P-glycoprotein (P-gp) and multidrug resistance-associated protein 2 (MRP2) in human gastrointestinal epithelial LS-180 cells. Furthermore, the functional activity of MRP2, using glutathione methylfluorescein (GS-MF) or [3H]methotrexate (MTX) as substrate, was investigated in canine kidney cells stably overexpressing human MRP2 (MDCK-MRP2). GTE, at a concentration of 0.01 mg/mL, did not increase mRNA expression of P-gp or MRP2 in LS-180 cells. Functional assays in MDCK-MRP2 cells using GS-MF did not show any effect of 0.01 mg/mL GTE on MRP2 activity. In the same cell line the cellular accumulation of MTX (a specific substrate of MRP2) was significantly increased with the MRP-specific inhibitor MK-571 or with 1 mg/mL GTE, but not with 0.1 mg/mL. The green tea components (-)-epigallocatechin gallate, (-)-epigallocatechin, theanine, or caffeine, each in corresponding concentrations to the respective concentration of GTE, did not show any effect on MRP2 function. These data demonstrate that the mRNA expression patterns of P-gp and MRP2 in LS-180 cells are not altered by 0.01 mg/mL of GTE. However, MRP2 function was inhibited by 1 mg/mL GTE, whereas none of the green tea components tested were responsible for this effect.
authors.affiliation: Department of Research and Clinical Pharmacology, University Hospital (Universitätsspital), Basel, Switzerland.
authors.forename: M I
authors.initials: MI
authors.lastname: Netsch
authors.forename: H
authors.initials: H
authors.lastname: Gutmann
authors.forename: S
authors.initials: S
authors.lastname: Luescher
authors.forename: S
authors.initials: S
authors.lastname: Brill
authors.forename: C B
authors.initials: CB
authors.lastname: Schmidlin
authors.forename: M H
authors.initials: MH
authors.lastname: Kreuter
authors.forename: J
authors.initials: J
authors.lastname: Drewe
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D028241:Camellia sinensis; D045744:Cell Line, Tumor / Q000187:drug effects; D017931:DNA Primers; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D006801:Humans; D049990:Membrane Transport Modulators; D026901:Membrane Transport Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D018515:Plant Leaves; D012333:RNA, Messenger / Q000032:analysis
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D017931:DNA Primers; D049990:Membrane Transport Modulators; D026901:Membrane Transport Proteins; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D010936:Plant Extracts; D012333:RNA, Messenger; C000715087:ABCC2 protein, human