The role of mitochondria in bee venom-induced apoptosis in human breast cancer MCF7 cells.
Our previous studies have shown that bee venom (BV) can induce apoptosis in human cervical cancer Ca Ski cells, but it can also affect human breast cancer cells, though its molecular mechanisms are not precisely known. In this study, the molecular mechanisms of apoptosis induced by BV in human breast cancer MCF7 cells were investigated. BV induced morphological changes (examined by phase-contrast microscopy) and inhibited the proliferation (examined by MTT assay) of MCF7 cells; both effects occurred in a dose- and time-dependent manner. Flow cytometric analysis demonstrated that BV induced the production of reactive oxygen species (ROS) and dysfunction of the mitochondrial membrane potential (Azm), and led to cytochrome c release, an increase in the levels of caspase-9 and Poly (ADP-ribose) polymerase (PARP) and then apoptosis. It also showed that BV induced S-phase arrest in MCF7 cells which may occur through the promotion of p53, p21, p27 and the exhibition of Cdk2. Western blotting demonstrated that BV reduced Bcl-2 and increased Bax protein levels which may have caused the changes of delta psi m. BV treatment led to ROS production up to but after treatment led to a decrease in the levels of ROS, which may be associated with the observations of BVaffecting glutathion S-transferase (GST), Zn-superoxide dismutase (Zn-SOD), Cu/Zn-superoxide dismutase (Cu/Zn-SOD) and catalase. The Comet assay also showed that BV induced DNA damage while DAPI staining also confirmed that BV induced apoptosis in examined MCF7 cells. Our results also showed that BV increased the levels of AIF and EndoG in MCF7 cells. In conclusion, our data demonstrated that BV induced apoptosis via a mitochondria-dependent pathway based on the changes of delta psi m, AIF and EndoG release in MCF7 cells.
Department of Nutrition, China Medical University, Taichung, Taiwan., , , , , , , , ,
Cell Line, Tumor
Cytochrome c Group
Dose-Response Relationship, Drug
Membrane Potential, Mitochondrial
Proto-Oncogene Proteins c-bcl-2
Reactive Oxygen Species
bcl-2-Associated X Protein
Pub Type(s)Journal Article
Research Support, Non-U.S. Gov't