title: Involvement of reactive oxygen species, but not mitochondrial permeability transition in the apoptotic induction of human SK-Hep-1 hepatoma cells by shikonin.
abstract: Shikonin has been demonstrated to exhibit anti-cancer activity, but the underlying mechanisms are poorly understood. In this report, we showed that the administration of shikonin could result in the induction of apoptotic cell death of human hepatoma cell line, SK-Hep-1. As evident by the flow-cytometric studies, shikonin has the capability of generating increased amounts of intracellular reactive oxygen species (ROS) during the early stage of this apoptotic process (ca. one-hour), and subsequently accompanied by the dissipation of mitochondrial transmembrane potential (deltapsi (m)) at 3 hours. Further studies indicated that this apoptotic process could effectively be protected by the pretreatment of shikonin-treated cells with glutathione (GSH) and N-acetylcysteine (NAC), a precursor of GSH, but not by cyclosporin A (CyA), an inhibitor of mitochondrial permeability transition (MPT) pore. These data further proved that ROS-mediated oxidative stress was the pivotal element involved in the induction of apoptosis of SK-Hep-1 cells. Taken together, we suggest that shikonin-induced apoptosis of SK-Hep-1 cells proceeds by an oxidative stress-mediated pathway.
authors.affiliation: Department of Medical Technology, Fooyin University, Ta-Liao, Kaohsiung, Taiwan, ROC.
authors.forename: Ching-Hsein
authors.initials: CH
authors.lastname: Chen
authors.forename: Chi-Liang
authors.initials: CL
authors.lastname: Chern
authors.forename: Chun-Ching
authors.initials: CC
authors.lastname: Lin
authors.forename: Fung-Jou
authors.initials: FJ
authors.lastname: Lu
authors.forename: Ming-Kuei
authors.initials: MK
authors.lastname: Shih
authors.forename: Pei-Ying
authors.initials: PY
authors.lastname: Hsieh
authors.forename: Tsan-Zon
authors.initials: TZ
authors.lastname: Liu
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D020287:In Situ Nick-End Labeling; D029684:Lithospermum; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009285:Naphthoquinones / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D008517:Phytotherapy; D018517:Plant Roots; D017382:Reactive Oxygen Species / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D009285:Naphthoquinones; D017382:Reactive Oxygen Species; C016101:shikonin