Murrayanine suppresses the proliferation and metastasis of human breast cancer cells via induction of apoptosis and inhibition of RANK/RANKL signaling pathway

摘要

Murrayanine and its derivatives have been shown to exhibit anticancer activities against different types of human cancer cells. However, the effects of murrayanine on the proliferation and metastasis of breast cancer cells are yet to be studied. The present study was designed to evaluate the effects of murrayanine on the proliferation and metastasis of human breast cancer via regulation of RANK/RANKL pathway. The results showed RANK/RANKL pathway to be highly activated in human breast cancer tissues and cell lines. However, treatment of the CAMA-1 breast cancer cells with murrayanine (0, 9, 18 and 36?μM) caused a significant (P??0.05) decline in the expression of RANK, RANKL and OPG in CAMA-1 cells. Additionally, murrayanine inhibited the growth of CAMA-1 cells with an IC50 of 18?μM. The antiproliferative of murrayanine were found be due to its ability to inhibit the expression of RANK, RANKL and OPG in CAMA-1 cells. To unveil if murrayanine exerted its effects via inhibition of RANK/RANKL pathway, the expression of RNAK was knocked down in CAMA-1 cells. It was found that murrayanine and RANK silencing both inhibited the growth CAMA-1 cells via induction of apoptosis. Additionally, murrayanine and RANK silencing both inhibited the migration, invasion and epithelial to mesenchymal transition of the CAMA-1 cells. Taken together, murrayanine exhibits significant anticancer activity against the breast cancer cells via induction of apoptosis and inhibition of RANK/RANKL signaling pathway. These findings suggest that murrayanine may prove to be a beneficial lead molecule for the development of breast cancer chemotherapy.