The effects of quercetin and kaempferol on multidrug resistance and the expression of related genes in human erythroleukemic K562/A cells

Abstract

Leukemia chemotherapy is believed to be impeded by multidrug resistance (MDR). Some compounds of flavonoid molecules were previously shown to inhibit drug transporter Pgp or induce apoptosis to sensitize MDR tumors. In this study, we attempted to investigate the possibility and mechanism of quercetin and kaempferol, flavonoid molecules, in reversing MDR. K562/A cells were cultured in vitro with the flavonoids as single and in combination respectively. Cell growth inhibition and adriamycin (ADR) sensitivity were detected by 3-[4,5-dimethylthiazol-2-yl]-2,5 -diphenyltetrazolium bromide (MTT) assay. Cell apoptosis was examined by Annexin V/PI staining method. Moreover, the expression of related genes for drug transporters and apoptosis was also tested after incubation with resveratrol for the first time. Results show a dose dependent manner and synergistic effect of the two compounds on K562/A. Furthermore, some of the genes in drug transporter families such as ATP-binding cassette (ABC) and solute carrier (SLC) and apoptosis related genes such as Bcl-2、tumor necrosis factor (TNF) and tumor necrosis factor receptor (TNFR) families were regulated. The experiment indicates that quercetin and kaempferol may be used as reveratrol in leukemia chemotherapy, but their interaction and difference should be noticed.

Key words: Flavonoids, leukemia, multidrug resistance, polymerase chain reaction (PCR) array.