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

Jingnan Zhang,Feng Wang,Gengbao Qu,Baokai Wang

doi:10.1186/s13765-021-00599-1

Jingnan Zhang, Feng Wang + Show 2 more

Open Access

https://doi.org/10.1186/s13765-021-00599-1

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Abstract

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.

Highlights

Breast cancer is one of the most frequent gynecological disorders which can be understood by the fact that more than 1.5 million females are diagnosed with this malignancy each year throughout the globe which sums up to nearly the 25% of total annually reported cancer cases in women [1, 2]
RANK/RANKL signaling pathway is over‐expressed in breast cancer The western blot analyses of RANK, RANKL and OPG proteins were performed from breast cancer and normal adjacent tissues
The RANK, RANKL and OPG protein and gene expression levels were determined from two breast cancer cell lines (SK-BR-3 and CAMA-1) and a normal breast epithelial cell line, MB-157

Summary

Introduction

Breast cancer is one of the most frequent gynecological disorders which can be understood by the fact that more than 1.5 million females are diagnosed with this malignancy each year throughout the globe which sums up to nearly the 25% of total annually reported cancer cases in women [1, 2]. Murrayanine is a carbazole type of plant-based alkaloid which is isolated from the bark of the stem of Murraya koenigii Spreng [6]. It has been given as a treatment for human cancer in traditional Chinese system [7]. Recent studies have shown that murrayanine and its derivatives exhibit considerable anti-proliferative effects against the human cancer cells [8–10]. Some murrayanine-Schiff ’s base derivatives have been shown to exhibit potent anticancer effects [9, 10]. Murrayanine targeted the RANK/RANKL signaling pathway which was shown to be highly active in breast cancer tissues and cells. The present study established the anticancer activity of murrayanine against breast cancer cells via the inhibition of RANK/RANKL signaling pathway

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