[Restorative effect of quercetin on subcellular distribution of daunorubicin in multidrug resistant leukemia cell lines K562/ADM and HL-60/ADM].
Xun Cai, Fangyuan Chen, Jie-Ying Han, Chun-Hong Gu, Hua Zhong, Ouyang Ren-rong
Abstract
Xun Cai, Fangyuan Chen, Jie-Ying Han, Chun-Hong Gu, Hua Zhong, Ouyang Ren-rong
Abstract
BACKGROUND & OBJECTIVE: Quercetin, a widely distributed natural flavonoid with a variety of biological functions, can reverse multidrug resistance (MDR) in leukemia according to recent researches. This study was to investigate the mechanism of quercetin restoring subcellular distribution of daunorubicin (DNR) in multidrug resistant leukemia cell lines, K562/ADM and HL-60/ADM, and reversing their MDR. METHODS: MTT cell viability assay was used to verify the sensitization of DNR by quercetin in K562/ADM and HL-60/ADM cells,and determine the reverse concentration extent,confocal laser scanning microscope was used to observe the subcellular distribution of DNR in K562/ADM and HL-60/ADM cells,and relevant sensitive cell lines, K562/S and HL-60/S,before and after quercetin exposion. RESULTS: Compared with K562/S and HL-60/S cells,20-40 micromol/L of quercetin in vitro remarkably enhanced the sensitivity of K562/ADM and HL-60/ADM cells to DNR, restore the subcellular distribution of DNR, so as to reverse MDR. CONCLUSION: quercetin could be a candidate of effective multidrug resistance-reversing agent in leukemia chemotherapy.
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BACKGROUND & OBJECTIVE: Quercetin, a widely distributed natural flavonoid with a variety of biological functions, can reverse multidrug resistance (MDR) in leukemia according to recent researches. This study was to investigate the mechanism of quercetin restoring subcellular distribution of daunorubicin (DNR) in multidrug resistant leukemia cell lines, K562/ADM and HL-60/ADM, and reversing their MDR. METHODS: MTT cell viability assay was used to verify the sensitization of DNR by quercetin in K562/ADM and HL-60/ADM cells,and determine the reverse concentration extent,confocal laser scanning microscope was used to observe the subcellular distribution of DNR in K562/ADM and HL-60/ADM cells,and relevant sensitive cell lines, K562/S and HL-60/S,before and after quercetin exposion. RESULTS: Compared with K562/S and HL-60/S cells,20-40 micromol/L of quercetin in vitro remarkably enhanced the sensitivity of K562/ADM and HL-60/ADM cells to DNR, restore the subcellular distribution of DNR, so as to reverse MDR. CONCLUSION: quercetin could be a candidate of effective multidrug resistance-reversing agent in leukemia chemotherapy.
Key concepts: Daunorubicin, K562 cells, Multiple drug resistance, Leukemia, Pharmacology, Quercetin, Chemistry, MTT assay