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

来源：

CANCER LETTERS | 2002年 / 177卷 / 01期

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

页码：89 / 93

页数：5

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