Berberine alkaloids inhibit the proliferation and metastasis of breast carcinoma cells involving Wnt/β-catenin signaling and EMT

Abstract

Berberine alkaloids belong to the class of isoquinoline alkaloids that have been shown to possess anticancer potential, berberine exhibits inhibitory effects on breast cancer development. However, the exact mechanisms of action for anti-breast carcinoma of the alkaloids, including epiberberine, berberrubine and dihydroberberine are still unclear. MTT assay, colony formation, wound healing and transwell invasion assays detected these alkaloids suppressed proliferation, migration and invasion of breast cancer cells. Hoechst and Annexin V-FITC/PI staining were used to analyze the apoptosis of breast cancer cells. Western blotting investigated the changes noted in the expression levels of the key proteins involved in the Wnt/β-catenin signaling pathway and epithelial to mesenchymal transition (EMT). The results showed that inhibited the proliferation of breast cancer cells. Berberine alkaloids inhibited the cell cycle at G2/M phase in MCF-7 cells, but in MDA-MB-231 cells berberine alkaloids arrested the cell cycle in G0/G1 and G2/M phases. By decreasing β-catenin expression, increasing GSK-3β expression and decreasing N-cadherin expression, increasing E-cadherin expression, which proved that epiberberine, berberrubine and dihydroberberine inhibited of metastasis of breast cancer cells through Wnt signaling pathway and reversed EMT except berberine. Furthermore, berberine alkaloids exert their anti-breast cancer effects through the synergistic action of intrinsic and extrinsic pathways of apoptosis. These findings highlight the different effects of different berberine alkaloids on breast cancer cells and confirm that berberine alkaloids may be potentially used in the treatment of breast cancer.