Breast cancer is one of the most lethal malignancies in the world. Oxymatrine is the major effective and toxic alkaloid component which is derived from the root of Sophora flavescens AIT, a traditional Chinese medicine which is widely distributed in Asia and the Pacific Islands. In the current research study, we investigated the effects and mechanisms of action of oxymatrine on breast cancer cells. We demonstrated that the viability and single cell proliferation capability of MCF-7 and MDA-MB-231, two breast cancer cell lines which are widely used in in vitro study, were significantly suppressed in a time-and concentration-dependent manner. Furthermore, the cell cycle of breast cancer cells treated with oxymatrine was arrested at the Sphase of the cell cycle. Oxymatrine also triggered apoptosis in breast cancer cells by modulating apoptosisrelated proteins, such as cleaved Caspase-3, cleaved Caspase-9 and poly(ADP-ribose) polymerase (PARP). The remarkable reduction in the ratio of Bcl-2/Bax was also observed in oxymatrine treated breast cancer cells.In conclusion, our research demonstrated that oxymatrine plays a critical role in suppressing carcinogenesis of breast cancer cells through cell cycle arrest and induction of mitochondria-mediated apoptosis, which suggests a promising application of this drug in breast cancer therapy.Key words oxymatrine; apoptosis; breast cancer; cell cycle Breast cancer is the most highly prevalent and diagnosed carcinoma in women worldwide and is the leading cause of cancer deaths in women, with approximately 500000 newly diagnosed cases reported in 2012.1) Currently, the main treatment options for breast cancer cases include surgery, radiotherapy, chemotherapy, hormone and immunological therapy. Although effectiveness could be observed in breast cancer patients receiving a variety of therapies, the high toxicity of these treatments to normal tissues is practically inevitable. Furthermore, breast cancer cells often propagate distant metastases and multi-drug resistance, which represents a main cause for treatment failure in cancer patients.2-4) Thus, the search for novel effective therapies and targeted drugs are an urgent priority with the aim of improving the efficacy of breast cancer treatment.Traditional Chinese medicine has been shown to be a fertile source of novel drug discovery. Many active components which are extracted from traditional Chinese herbs exhibit effects in many human diseases.5-7) For example, oxymatrine is the main effective and toxic alkaloid component derived from the root of Sophora flavescens AIT, which is widely distributed in Asia and the Pacific Islands.8-10) It was previously reported that oxymatrine displays specific pharmacological effects in targeting hepatitis B infections and liver fibrosis. [11][12][13] Furthermore, it has been demonstrated that oxymatrine exerts anti-tumor properties in several cancers via different signaling pathways, such as suppression of proliferation and promotion of apoptosis. [14][15][16][17] Although previous studies s...