Costunolide Induce Apoptosis by ROS-mediated Mitochondrial Permeability Transition anb Cytochrome C Release

概要

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Consunolide is an active compound isolated from the root of Saussurea lappa Clarks, a Chinese medicinal harb, and 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 ocygen species(ROS), and asessment of mitochondrial membrane potentials, we show that costunolide is a optent inducer of apoptosis, and facilitates its activit via ROS generation, theraby inducing mitochondrial permeability transition(MPT)and ytochrome c release to the cyrosol. ROS production, mitochondrial alteration, and subsequent apoptotic cell death in constunolide-treated cells were blocked by the antioxidant N-acetylcystein(NAC). Cyclosporin A, a permeability transition inhibitor, also inhibited mitochondrial perability transition and apoptosis. Our data indicate that constunolide induces the ROS-midiated mitochodrial permeability transition and resultant cytoshome c release. This is the first report on the mechanism of the anticancer efefect of constunolide
公益社団法人日本薬学会の論文
2001-03-01