Inhibition of P-glycoprotein by flavonoid derivatives in adriamycin-resistant human myelogenous leukemia (K562/ADM) cells

被引:59
作者
Ikegawa, T
Ohtani, H
Koyabu, N
Juichi, M
Iwase, Y
Ito, C
Furukawa, H
Naito, M
Tsuruo, T
Sawada, Y [1 ]
机构
[1] Kyushu Univ, Grad Sch Pharmaceut Sci, Dept Medicopharmaceut Sci, Higashi Ku, Fukuoka 8128582, Japan
[2] Mukogawa Womens Univ, Fac Pharmaceut Sci, Nishinomiya, Hyogo 6638179, Japan
[3] Meijo Univ, Fac Pharm, Tempa Ku, Nagoya, Aichi 4688503, Japan
[4] Univ Tokyo, Inst Mol & Cellular Biosci, Bunkyo Ku, Tokyo 1130032, Japan
关键词
flavonoid derivatives; P-glycoprotein; vincristine; multidrug resistance;
D O I
10.1016/S0304-3835(01)00761-3
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
We investigated the effects of natural flavones, quercetin and morin, and their pentamethyl, pentaethyl, pentapropyl, pentabutyl and pentaallyl ethers, on the function of P-glycoprotein (P-gp) assessed by an increase in the uptake of [H-3]vincristine by human myelogenous leukemia (K562) cells and adriamycin-resistant human myelogenous leukemia (K562/ADM) cells. Pentamethyl, pentaethyl, pentapropyl and pentaallyl ethers of morin and quercetin (20 muM) all increased the uptake of [H-3]vincristine by K562/ADM cells, while quercetin, morin and their pentabutyl ethers had no effect. Pentamethylquercetin, pentaallylquercetin and pentaethylmorin remarkably increased the uptake of [H-3]vincristine by K562/ADM cells by 10.6, 10.8 and 14.4-fold, respectively. These inhibitory potencies for P-gp were more potent than typical P-gp inhibitors, cyclosporine A and verapamil. Taking into consideration that these flavonoid derivatives possess antitumor promoter activity, they may become candidates of effective multidrug resistance-reversing agents in cancer chemotherapy. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.
引用
收藏
页码:89 / 93
页数:5
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