Wnt/β-catenin signaling pathway is deregulated in colorectal carcinoma, and its central component β-catenin is the focus of many targeted anticancer therapies. In healthy cells, where the Wnt signaling pathway is not active, this protein is present in the peripheral part of the cytoplasm, bound to E-cadherin, thus forming a complex with a role in connecting neighboring cells, which reflects its importance in the epithelium tissue. If found free in the cytoplasm, it becomes immediately degraded by the APC complex. However, in cancer cells, the Wnt pathway is deregulated and if the APC is mutated or absent, β-catenin is not degraded. It becomes transported into nucleus where acts as transcription factor regulating cell proliferation, migration and invasion, thus formation of metastases. We examined the effect of the natural product, royal jelly (RJ) on β-catenin, since previous studies have shown that RJ has certain suppressive properties on cancer, as well as on its progression in terms of metastasis.

In this study, we examined the effects of two RJ concentrations after 24 h on gene expression of this marker using the qRT-PCR method, while the levels and localization of protein fractions in the nucleus and cytoplasm were evaluated by immunofluorescence technique.

The results showed that this natural treatment caused increase in β-catenin gene expression in a dose-dependent manner, compared to the level of the control housekeeping gene β-actin. However, regarding protein expression, RJ significantly decreased the level of nuclear β-catenin, while simultaneously increasing the values ​​of its cytoplasmic fraction. Immunofluorescence also showed its membrane localization, implying its involvement in intercellular connections. The results presented indicate that the treatment caused the export of β-catenin from the nucleus to the cytoplasm and migration to the membrane in order to bind to E-cadherin and restore intercellular connections, which is a significant result of our study.