Combination of quercetin and hyperoside inhibits prostate cancer cell growth and metastasis via regulation of microRNA-21

Previous studies have reported that hyperoside and quercetin in combination (QH; 1:1) inhibited the growth of human leukemia cells. The aim of the present study was to investigate the anti-cancer effect of QH on prostate cancer cells. The results demonstrated that QH decreased the production of reactive oxygen species (ROS) and increased antioxidant capacity in PC3 cells at various concentrations (2.5-60 mu g/ml) with peak inhibition and augmentation changes of 3.22- and 3.00-fold, respectively. Following treatment with QH for 48 and 72 h, the IC50-values on PC3 cells were 19.7 and 12.4 mu g/ml, respectively. Western blot analysis revealed that QH induced apoptosis in human prostate cancer cells via activation of caspase-3 and cleavage of poly(adenosine diphosphate ribose) polymerase. In addition, QH significantly inhibited the invasion and migration of PC3 cells as well as reduced the expression of numerous prostate tumor-associated microRNAs (miRs), including miR-21, compared to that of untreated human prostate cancer cells. QH was also found to enhance the expression of tumor suppressor programmed cell death protein 4, which was negatively regulated by miR-21. Furthermore, induced overexpression of miR-21 using pre-miR-21 oligonucleotides attenuated the beneficial effect of QH on prostate cancer cells. In conclusion, the results of the present study indicated that QH exerted an anti-cancer effect on human prostate cancer cells, the mechanism of which proceeded, at least in part, via the inhibition of the miR-21 signaling pathway.