Involvement of multidrug resistance-associated proteins in regulating cellular levels of (-)-epigallocatechin-3-gallate and its methyl metabolites

被引：146

作者：

Hong, J

Lambert, JD

Lee, SH

Sinko, PJ

Yang, CS ^{[1
]}

机构：

[1] Rutgers State Univ, Ernest Mario Sch Pharm, Dept Biol Chem, Susan Lehman Cullman Lab Canc Res, Piscataway, NJ 08854 USA

[2] Rutgers State Univ, Ernest Mario Sch Pharm, Dept Pharmaceut, Piscataway, NJ 08854 USA

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2003年 / 310卷 / 01期

关键词：

EGCG; efflux; Pgp; MRP; MDCKII cell;

D O I：

10.1016/j.bbrc.2003.09.007

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

(-)-Epigallocatechin-3-gallate (EGCG), a major polyphenol of green tea, has many interesting biological activities. The uptake of EGCG and involvement of specific efflux pumps were studied in MDCKII cells transfected with hPgp, hMRP1, and hMRP2 genes. Total cell associated [H-3]EGCG increased 7-fold in the presence of the MRP inhibitors, indomethacin and probenecid, in MDCKII/MRP1 cells, compared to a 2-fold increase in wild-type cells. Intracellular levels of EGCG, 4"-O-methyl EGCG, and 4',4"-di-O-methyl EGCG were increased by 13-, 11-, and 3-fold, respectively, by indomethacin in MDCKII/MRP1 cells. Accumulation of EGCG and its methyl metabolites was also increased similar to10-fold in the presence of MK-571 in MDCKII/MRP2 cells. Co-treatment with isoflavones, curcumin and tetrahydrocurcumin, increased [H-3]EGCG accumulation significantly in MDCKII/MRP1 and HT-29 cells. The results indicate that EGCG and its methyl metabolites are substrates for MRP1 and MRP2, but not for Pgp. MRP type efflux pumps may limit the bioavailability of EGCG. (C) 2003 Elsevier Inc. All rights reserved.

引用

页码：222 / 227

页数：6

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