Brevilin A promotes oxidative stress and induces mitochondrial apoptosis in U87 glioblastoma cells

Background: Sesquiterpene lactones are plant-derived, natural, bioactive molecules often used against inflammatory diseases in traditional Chinese medicines. Recently, sesquiterpene lactones have been reported to exhibit potent anticancer activity. In the present study, we have investigated the anticancer activity of Brevilin A, a sesquiterpene lactone component of Centipeda minima, against U87 glioblastoma cells. Materials and methods: The cell proliferation was determined by MTT assay. Cell morphological changes were observed by phase-contrast microscopy. Flow cytometry was used to measure apoptosis. Glutathione (GSH), ROS generation, and mitochondrial membrane potential were measured using commercially available kits. The expression of proteins was measured by Western blotting analysis. Results: Brevilin A inhibited the proliferation of, and induced severe morphological changes and apoptotic cell death in, U87 glioblastoma cells in a dose-dependent manner. Further mechanistic study revealed that Brevilin A induces oxidative stress, as evident from ROS generation, GSH depletion, and increased phosphorylation of stress-activated proteins p38 and JNK. Furthermore, Brevilin A bcl-xl/bak ratio, decreased mitochondrial membrane potential and induced cytochrome c release from mitochondria into cytosol in a dose-dependent manner. Finally, Brevilin A decreased the expression of Xiap and increased the expression of cleaved forms of caspase-9 and -3 and PARP in a dose-dependent manner. Conclusion: Collective findings demonstrated that Brevilin A is a potent, anticancer, bioactive molecule and it effectively induces apoptosis in U87 glioblastoma cells, which is associated with induction of oxidative stress and mitochondrial dysfunction.