BACKGROUND: Sanguinarine is a benzophenanthridine alkaloid derived from the root of Sanguinaria canadensis, which induces apoptosis in human cancer cells, but the underlying action mechanisms are not completely understood. We investigated the mechanisms of sanguinarine on the induction of apoptosis using U937 leukemia cells. METHODS: Cytotoxicity was evaluated by MTT assay. Apoptosis was detected using DAPI staining, agarose gel electrophoresis and flow cytometry. The protein levels were

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... ned by Western blot analysis. Caspase-3 activity was measured using a colorimetric assay. RESULTS: Exposure of U937 cells to sanguinarine resulted in growth inhibition and induction of apoptosis. Apoptosis by sanguinarine treatment was associated with the activation of caspase-3 and degradation of poly-(ADPribose) polymerase (PARP) and phospholipase C-gamma 1 protein. Induction of apoptosis by sanguinarine was also accompanied by upregulation of pro-apoptotic Bax and downregulation of antiapoptotic Bcl-2 expression. Sanguinarine-induced caspase-3 activation and apoptosis were significantly