Reversal of MRP-mediated doxorubicin resistance with quinoline-based drugs

被引:76
作者
Vezmar, M [1 ]
Georges, E [1 ]
机构
[1] McGill Univ, Inst Parasitol, Ste Anne De Bellevue, PQ H9X 3V9, Canada
关键词
multidrug resistance; chloroquine; multidrug resistance-associated protein (MRP); photoaffinity labeling; quinoline; MDR reversal;
D O I
10.1016/S0006-2952(00)00270-7
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The overexpression of P-glycoprotein (P-gp) and the multidrug resistance-associated protein (MRP) have been shown to confer broad drug resistance in tumor cells. We have demonstrated previously direct binding between MRP and a quinoline-based photoreactive drug (iodo-azido-amino quinoline, IAAQ) (Vezmar et al., Biochem Biophys Res Commun 241: 104-111, 1997). In this report, we show the reversal of multidrug resistance in two MRP-overexpressing cell lines, HL60/AR and H69/AR, with four quinoline-based drugs. Non-toxic concentrations (5-20 mu M) of chloroquine, quinine, quinidine, and primaquine potentiated the toxicity of doxorubicin in a concentration-dependent manner. These quinoline-based drugs showed a 5- to 10-fold decrease in the re, of doxorubicin in H69/AR and HL60/AR cells. Primaquine was the most active, with modulation ratios of 10- and 5-fold versus 8- and 3-fold with MK-571 for H69/AR and HL60/AR, respectively. Moreover, using IAAQ, we showed that molar excesses of chloroquine, quinine, quinidine, and MK-571 inhibit the photoaffinity labeling of MRP. Primaquine and vinblastine showed lesser inhibition of MRP photoaffinity labeling by IAAQ. Taken together, the results of this study demonstrated the reversal of doxorubicin resistance with several quinoline-based drugs. Moreover, these drugs have been shown to reverse P-gp-mediated MDR and are clinically well tolerated. (C) 2000 Elsevier Science Inc.
引用
收藏
页码:1245 / 1252
页数:8
相关论文
共 72 条
[1]   CHEMOSENSITISATION OF SPONTANEOUS MULTIDRUG-RESISTANCE BY A 1,4-DIHYDROPYRIDINE ANALOG AND VERAPAMIL IN HUMAN GLIOMA CELL-LINES OVEREXPRESSING MRP OR MDR1 [J].
ABE, T ;
KOIKE, K ;
OHGA, T ;
KUBO, T ;
WADA, M ;
KOHNO, K ;
MORI, T ;
HIDAKA, K ;
KUWANO, M .
BRITISH JOURNAL OF CANCER, 1995, 72 (02) :418-423
[2]   PHASE-I TRIAL OF DOXORUBICIN WITH CYCLOSPORINE AS A MODULATOR OF MULTIDRUG-RESISTANCE [J].
BARTLETT, NL ;
LUM, BL ;
FISHER, GA ;
BROPHY, NA ;
EHSAN, MN ;
HALSEY, J ;
SIKIC, BI .
JOURNAL OF CLINICAL ONCOLOGY, 1994, 12 (04) :835-842
[3]   HIGH MDR1- AND MRP-, BUT LOW TOPOISOMERASE-II ALPHA-GENE EXPRESSION IN B-CELL CHRONIC LYMPHOCYTIC LEUKEMIAS [J].
BECK, J ;
NIETHAMMER, D ;
GEKELER, V .
CANCER LETTERS, 1994, 86 (01) :135-142
[4]   NOVEL ACTIONS OF INHIBITORS OF DNA TOPOISOMERASE-II IN DRUG-RESISTANT TUMOR-CELLS [J].
BECK, WT ;
KIM, R ;
CHEN, M .
CANCER CHEMOTHERAPY AND PHARMACOLOGY, 1994, 34 :S14-S18
[5]   PHOTOAFFINITY SUBSTRATES FOR P-GLYCOPROTEIN [J].
BECK, WT ;
QIAN, XD .
BIOCHEMICAL PHARMACOLOGY, 1992, 43 (01) :89-93
[6]   MRP GENE OVEREXPRESSION IN A HUMAN DOXORUBICIN-RESISTANT SCLC CELL-LINE - ALTERATIONS IN CELLULAR PHARMACOKINETICS AND IN PATTERN OF CROSS-RESISTANCE [J].
BINASCHI, M ;
SUPINO, R ;
GAMBETTA, RA ;
GIACCONE, G ;
PROSPERI, E ;
CAPRANICO, G ;
CATALDO, I ;
ZUNINO, F .
INTERNATIONAL JOURNAL OF CANCER, 1995, 62 (01) :84-89
[7]   ONE-ELECTRON REDUCTION OF THE ANTIMALARIAL DRUG PRIMAQUINE, STUDIED BY PULSE-RADIOLYSIS [J].
BISBY, RH .
FREE RADICAL RESEARCH COMMUNICATIONS, 1988, 5 (02) :117-124
[8]   CLASSICAL AND NOVEL FORMS OF MULTIDRUG-RESISTANCE AND THE PHYSIOLOGICAL FUNCTIONS OF P-GLYCOPROTEINS IN MAMMALS [J].
BORST, P ;
SCHINKEL, AH ;
SMIT, JJM ;
WAGENAAR, E ;
VANDEEMTER, L ;
SMITH, AJ ;
EIJDEMS, EWHM ;
BAAS, F ;
ZAMAN, GJR .
PHARMACOLOGY & THERAPEUTICS, 1993, 60 (02) :289-299
[9]  
Chan HSL, 1997, CANCER RES, V57, P2325
[10]   P-GLYCOPROTEIN EXPRESSION AS A PREDICTOR OF THE OUTCOME OF THERAPY FOR NEUROBLASTOMA [J].
CHAN, HSL ;
HADDAD, G ;
THORNER, PS ;
DEBOER, G ;
LIN, YP ;
ONDRUSEK, N ;
YEGER, H ;
LING, V .
NEW ENGLAND JOURNAL OF MEDICINE, 1991, 325 (23) :1608-1614