Ruttiros Khonkarn,
Chiang Mai University, Thailand
Title: Overcoming multidrug resistant cancer cells with polymeric micelles of the flavonoids of the Zingiberaceae
Biography
Biography: Ruttiros Khonkarn,
Abstract
Zingiberaceous plants have been used in traditional medicines throughout the tropical countries. The Zingiberaceae is rich in flavonoids especially quercetin and its derivatives. Flavonoids are potent antioxidant compounds with excellent anticancer activity. Inhibition of multidrug resistant cancer cell growth and MDR transporter by flavonoids has been reported. In this study, the water-insoluble quercetin was loaded into mPEG-b-OCL-Bz micelles. The average particle size of quercetin-loaded mPEG-b-OCL-Bz micelles was around 14-20nm with a maximum loading capacity of 7.3%. Besides, quercetin incorporated polymeric micelles are stable for 14 days at 37℃. The cytotoxicity results of this study reveal that the similar cell growth inhibition on sensitive and resistant leukemia cells was found from both free quercetin and quercetin loaded micelles which suggested that free quercetin and quercetin-loaded micelles were not transported by P-glycoprotein. Interestingly, QCT-loaded micelles increased the efficacy of the cytotoxicity of chemotherapeutic drugs (doxorubicin and daunorubicin) indicating that QCT-loaded micelle can reverse the function of P-glycoprotein. Finally, the determination of the kinetics of P-glycoprotein found that the efflux of pirarubicin was modulated by quercetin-loaded micelles in a dose-dependent manner and non-competitive mechanism. These results demonstrated that mPEG-b-OCL-Bz micelles are a promising carrier for overcoming multidrug resistance cancer.