[Reversal of multidrug resistance of HL-60 adriamycin resistant leukemia cell line by quercetin and its mechanisms].
OBJECTIVE
Quercetin, 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.


METHODS
MTT 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.


RESULTS
Compared 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.


CONCLUSIONS
Quercetin could be a candidate of effective multidrug resistance-reversing agent with low toxicity in leukemia chemotherapy.
Cai
Xun
X
Shanghai No.6 People's Hospital, Department of Oncology, Shanghai Jiaotong University, Shanghai 200233, China. caixuncn@yahoo.com.cn
Chen
Fang-yuan
FY
Han
Jie-ying
JY
Gu
Chun-hong
CH
Zhong
Hua
H
Teng
Ye
Y
Ouyang
Ren-rong
RR
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000187:drug effects; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000187:drug effects; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D003630:Daunorubicin / Q000494:pharmacology*; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D018922:HL-60 Cells; D006801:Humans; D011794:Quercetin / Q000494:pharmacology*
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000903:Antibiotics, Antineoplastic; D011794:Quercetin; D003630:Daunorubicin