Effect of oxymatrine on the side population and expression of β-catenin in MCF-7 breast cancer cells.

Abstract

e13505 Background: The cancer stem cells (CSCs) play a critical role in both cancer initiation and relapse as they are resistant to most of cytotoxic agents and able to proliferate indefinitely. The recent identification of CSCs in multiple human cancers provides a new inroad to understanding tumorigenesis at the cellular level. Oxymatrine is an alkaloid compound found in plants that display anti-microbial and anti-inflammatory activities. And also has been demonstrated to have the anti-tumor effects. Since to date, very few treatments have targeted cancer stem-like cells, so the detection of CSCs in breast cancer leads us to investigate whether oxymatrine might affect the CSCs specifically. Methods: Cytotoxicity and cancer stem-like cells (side population, SP) identification and sorting were performed. Inhibitory effect was evaluated on the sorted SP and non-SP cells. At the same time, β-catenin, phosphorylated β-catenin, c-myc and cyclinD1 were also detected by fluorescence microscope, FACS, Western blot and fluorescence quantitative PCR among oxymatrine treated MCF-7 and the control one. Cisplatin was the positive control drug of these experiments. Results: SP cells were identified with percentage (3-5%) in MCF-7 cells. Oxymatrine caused a dose-dependent reduction in the proliferation of MCF-7 cells and a decrease in SP cells relative to untreated controls. As compared to non-SP cells, inhibitory effect in the SP cells was higher. Wnt/β-catenin signaling pathway was also examined by analyzing the expression of totalβ-catenin and phosphorylatedβ-catenin in cytoplasm, oxymatrine treatment was associated with an inhibition of Wnt/β-catenin signaling pathway relative to untreated controls. Conclusions: These results indicate that the growth inhibitory effects of oxymatrine treatment on MCF-7 cells may be partly via effects on SP and Wnt/β-catenin signaling pathway. Further work is warranted to explore whether oxymatrine may be a useful novel therapeutic drug for targeting breast CSCs.