Sanguinarine, a benzophenanthridine alkaloid derived from the root of Sanguinaria canadendid, has been shown to possess anti-microbial, anti-inflammatory, and anti-oxidant properties. In recent studies, this compound also has been shown to have cytotoxic activity in some cancer cells however its mechanisms on malignant cell growth are not known. In the present study, we investigated the mechanism of apoptosis induced by sanguinarine in human breast carcinoma MCF-7 cells. Sanguinarine induced cytotoxicity, cell cycle modulation and apoptosis in MCF-7 cells in a concentration dependent manner, as measured by MTT assay, microscopy and flow cytometry analysis. The anti-proliferative effects and apoptosis induced by sanguinarine were associated with up-regulation of tumor suppressor p53 and cyclin-dependent kinase inhibitor p21, degradation of poly-(ADP-ribose) polymerase and generation of reactive oxygen species (ROS). N-acetyl-L-cysteine, a ROS scavenger, blocked p53 and p21 induction, and significantly attenuated sanguinarine-induced apoptosis. These results show that sanguinarine potently induces apoptosis in MCF-7 cells and sanguinarine-induced apoptosis is related to the ROS generation. (Cancer Prev Res 12, 192-199, 2007)

Keywords: Sanguinarine, p53, p21, Reactive oxygen species