Reversal of Multidrug Resistance in Human Leukemia Cells by Quercetin

다국어 초록 (Multilingual Abstract)

Development of multidrug resistance (MDR) is a major obstacle for successful chemotherapy of many human cancers. The main characteristics of tumor cells displaying the MDR are cross-resistance to structually unrelated cytotoxic drugs having different mechanisms of action. This resistance can be due to different factors, including failure of drug uptake or activation, alteration in the level of target enzyme such as topoisomerase II and increased anticancer drug efflux. This last mechanism of resistance apprears to be a major one and is usually linked to the overexpression of P-glycoprotein (P-gp), a plasma trans-membrane glycoprotein encoded by MDR1 genes and thought to act as an ATP-dependent drug efflux pump. Although, the mechanism involved in the regulation of P-gp expression are still unclear, the expression of P-gp appears to be controlled by protein kinase C(PKC). Thid study evaluated the influence of Quercetin on the cytotoxicity of anticancer drugs in K562/ADR cells. Quercetin (3,3’,4’,5,7-pentahydroxyflavone) is one of the most widely distributed flavonoids in nature. Numerous studies have revealed diverse biological effects of quercein, including protein kinase C inhibition. In this experiment, quercein almost completely inhibited the expression of PKC. It enhanced the cytotoxic effects of not only adriamicin but also taxol in K562/ADR cells. The expression of P-gp was inhibited by quercetin in a dose-dependent manner. In addition, quercein also increased adriamycin accumulation and slowed down the efflux of rhodamine-123 from K562/ADR cells. Our results suggrst that quercetin can be a modulator of MDR which could be used for a combination chemotherapy in cancer treatment.