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

被引:89
作者
Ikegawa, T
Ushigome, F
Koyabu, N
Morimoto, S
Shoyama, Y
Naito, M
Tsuruo, T
Ohtani, H
Sawada, Y
机构
[1] Kyushu Univ, Grad Sch Pharmaceut Sci, Dept Biopharmaceut, Higashi Ku, Fukuoka 8128582, Japan
[2] Univ Tokyo, Inst Mol & Cellular Biosci, Bunkyo Ku, Tokyo 1130032, Japan
关键词
grapefruit juice; orange juice; methoxyflavone; vincristine; multidrug resistance; cancer chemotherapy;
D O I
10.1016/S0304-3835(00)00549-8
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 [H-3]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 [H-3]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 [H-3]vincristine, resulting in the intracellular accumulation of chamotherapeutic drugs. These components may become candidates of multi-drug resistance reversing agents in cancer chemotherapy. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.
引用
收藏
页码:21 / 28
页数:8
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