Regulation of Wnt Signaling and Anti-cancer Effect of Propolis and Honey Mixture according to Filtering Condition

Among the various signal transduction processes in cells against cancer, the activated Wnt signal is activated through the initiation of an intracellular "disheveled" signal, and it is induced cancer through overexpression of intracellular TCF/LEF genes through GSK-3β and binding inhibition of β-catenin. GSK-3β and β-catenin were overexpressed which correspond to Wnt signaling pathway in PANC-1 cells as a pancreatic cancer cells. We prepared a mixed formulation called "honeypolis" that honey and propolis mixture. Through inhibition of PCNA expression and Akt phosphorylation, and increasing of ERK phosphorylation, honeypolis inhibited PANC-1 cell proliferation. However, honeypolis dose not exhibit apoptosis of PANC-1. This effect is caused by specific functional components in propolis and it was confirmed according to the mixing and filtering order of the honeypolis. Cytotoxicity evaluation showed that specific components had an effect on cell death, Western blotting confirmed that the reducing expression of GSK-3β, β-catenin and mTOR protein corresponding to activated Wnt signaling pathway in PANC-1. In addition, this effect has been shown to be enhanced by a mixture of honey and propolis more than honey and propolis only. This result means that honey and propolis mixture has synergistic effects and it can be regulates Wnt signal cascade on PANC-1. Therefore, we suggested that the honeybee products regulates cell functionality about molecular level and it can be used to possibility against cancer.