Costunolide is an active compound isolated from the root of Saussurea lappa Clarks, a Chinese medicinal herb, and is considered a therapeutic candidate 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 via ROS generation, thereby inducing mitochondrial permeability transition (MPT) and
cytochrome c release to the cytosol. ROS production, mitochondrial alteration, and subsequent apoptotic cell death in
costunolide-treated cells were blocked by the
antioxidant N-acetylcystein (NAC).
Cyclosporin A, a permeability transition inhibitor, also inhibited mitochondrial permeability transition and apoptosis. Our data indicate that
costunolide induces the ROS-mediated mitochondrial permeability transition and resultant
cytochrome c release. This is the first report on the mechanism of the anticancer effect of
costunolide.