Costunolide induces apoptosis by ROS-mediated mitochondrial permeability transition and cytochrome C release

Costunolide is an active compound isolated from the root of Saussurea lappa Clarks, a Chinese medicinal herb, and is considered a therapeutic candidat e for various types of cancers. Nevertheless, the pharmacological pathways of costunolide are still unknown. In this study, we investigate the effects of costunolide on the induction of apoptosis in HL-60 human leukemia cells and its putative pathways of action. Using apoptosis analysis, measurement of reactive oxygen species (ROS), and assessment of mitochondrial membrane potentials, we show that costunolide is a potent inducer of apoptosis, and facilitates its activity Pin ROS generation, thereby inducing mitochondria l permeability transition (MPT) and cytochrome c release to the cytosol, RO S production, mitochondrial alteration, and subsequent apoptotic cell death in costunolide-treated cells were blocked by the antioxidant N-acetylcyste in (NAC). Cyclosporin A, a permeability transition inhibitor, also inhibite d mitochondrial permeability transition and apoptosis, Our data indicate;ha t costunolide induces the ROS-mediated mitochondrial permeability transitio n and resultant cytochrome c release. This is the first report on the mecha nism of the anticancer effect of costunolide.