Inhibition of P-glycoprotein by orange juice components, polymethoxyflavones in adriamycin-resistant human myelogenous leukemia (K562/ADM) cells.

Abstract:

:We investigated the effects of the ethyl acetate extract of grapefruit juice (GFJ), that of orange juice (OJ) and their components on the uptake of [(3)H]vincristine into adriamycin-resistant human myelogenous leukemia cells. Its uptake was increased by the extracts of GFJ and OJ up to 7- and 3-fold, respectively, as well as verapamil and cyclosporin A. OJ components, i.e. 3,3',4',5,6,7,8-heptamethoxyflavone, nobiletin and tangeretin, also increased the uptake of [(3)H]vincristine in a concentration-dependent manner. Although GFJ components, dihydroxybergamottin and bergamottin, significantly increased the uptake, their potencies were considerably weaker than those of OJ components. These data suggest that OJ components inhibit P-gp-mediated efflux of [(3)H]vincristine, resulting in the intracellular accumulation of chemotherapeutic drugs. These components may become candidates of multi-drug resistance reversing agents in cancer chemotherapy.

journal_name

Cancer Lett

journal_title

Cancer letters

authors

Ikegawa T,Ushigome F,Koyabu N,Morimoto S,Shoyama Y,Naito M,Tsuruo T,Ohtani H,Sawada Y

doi

10.1016/s0304-3835(00)00549-8

keywords:

subject

Has Abstract

pub_date

2000-11-10 00:00:00

pages

21-8

issue

1

eissn

0304-3835

issn

1872-7980

pii

S0304-3835(00)00549-8

journal_volume

160

pub_type

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