Reversal of multidrug resistance of HL-60 adriamycin resistant leukemia cell line by quercetin and its mechanisms.
- Author:
Xun CAI
1
;
Fang-yuan CHEN
;
Jie-ying HAN
;
Chun-hong GU
;
Hua ZHONG
;
Ye TENG
;
Ren-rong OUYANG
Author Information
- Publication Type:Journal Article
- MeSH: ATP Binding Cassette Transporter, Sub-Family B; drug effects; ATP-Binding Cassette, Sub-Family B, Member 1; drug effects; Antibiotics, Antineoplastic; pharmacology; Daunorubicin; pharmacology; Drug Resistance, Multiple; drug effects; Drug Resistance, Neoplasm; drug effects; HL-60 Cells; Humans; Quercetin; pharmacology
- From: Chinese Journal of Oncology 2005;27(6):326-329
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVEQuercetin, a widely distributed natural flavonoid with a variety of biological functions, can reverse multidrug resistance (MDR) in leukemia according to recent researches. The aim of this study was to investigate the mechanisms of reversal of multi-drug resistance by quercetin mainly in respect of membrane transporters.
METHODSMTT cell viability assay was used to verify the chemo-sensitization to daunorubicin (DNR) by quercetin in HL-60/ADM cell line and determine the effective reversal concentration, the expression of MRP(1) gene and its protein product, multidrug resistant associated protein 1 by RT-PCR and flow cytometry By confocal laser scanning microscopy, the subcellular distribution of DNR in HL-60/S and HL-60/ADM cells was examined before and after quercetin exposure.
RESULTSCompared with HL-60/S, 20-40 micromol/L quercetin in vitro remarkably enhanced the sensitivity of HL-60/ADM cells to daunorubicin, down-regulated the expression of MRP(1) gene and its protein product MRP(1), restored the abnormal subcellular distribution of daunorubicin, so as to reverse MDR. Moreover, such an effective concentration of quercetin was non-toxic to the cells.
CONCLUSIONQuercetin could be a candidate of effective multidrug resistance-reversing agent with low toxicity in leukemia chemotherapy.
