title: Parthenolide-induced apoptosis of hepatic stellate cells and anti-fibrotic effects in an in vivo rat model.
abstract: Parthenolide (PT), a sesquiterpene lactone derived from the plant feverfew, has pro-apoptotic activity in a number of cancer cell types. We assessed whether PT induces the apoptosis of hepatic stellate cells (HCSs) and examined its effects on hepatic fibrosis in an in vivo model. The effects of PT on rat HSCs were investigated in relation to cell growth inhibition, apoptosis, NF-κB binding activity, intracellular reactive oxygen species (ROS) generation, and glutathione (GSH) levels. In addition, the anti-fibrotic effects of PT were investigated in a thioacetamide-treated rat model. PT induced growth inhibition and apoptosis in HSCs, as evidenced by cell growth inhibition and apoptosis assays. PT increased the expression of Bax proteins during apoptosis, but decreased the expression of Bcl-2 and Bcl-X(L) proteins. PT also induced a reduction in mitochondrial membrane potential, poly(ADP-ribose) polymerase cleavage, and caspase-3 activation. PT inhibited TNF-α-stimulated NF-κB binding activity in HSCs. The pro-apoptotic activity of PT in HSCs was associated with increased intracellular oxidative stress as evidenced by increased intracellular ROS levels and depleted intracellular GSH levels. Furthermore, PT ameliorated hepatic fibrosis significantly in a thioacetamide- treated rat model. In conclusion, PT exhibited pro-apoptotic effects in rat HSCs and ameliorated hepatic fibrosis in a thioacetamide-induced rat model.
authors.affiliation: Department of Internal Medicine, Research Institute of Clinical Medicine, Chonbuk National University Medical School and Hospital, Jeonju 561-712, Korea.
authors.forename: In Hee
authors.initials: IH
authors.lastname: Kim
authors.forename: Sang Wook
authors.initials: SW
authors.lastname: Kim
authors.forename: Seong Hun
authors.initials: SH
authors.lastname: Kim
authors.forename: Seung Ok
authors.initials: SO
authors.lastname: Lee
authors.forename: Soo Teik
authors.initials: ST
authors.lastname: Lee
authors.forename: Dae Ghon
authors.initials: DG
authors.lastname: Kim
authors.forename: Mi Jin
authors.initials: MJ
authors.lastname: Lee
authors.forename: Woo Hyun
authors.initials: WH
authors.lastname: Park
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015870:Gene Expression / Q000187:drug effects; D055166:Hepatic Stellate Cells / Q000187:drug effects*; D006801:Humans; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000188:drug therapy*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D012717:Sesquiterpenes / Q000008:administration & dosage*; D013853:Thioacetamide / Q000633:toxicity; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D051020:bcl-X Protein / Q000378:metabolism
chemical_list: C494828:Bax protein, rat; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D012717:Sesquiterpenes; D014409:Tumor Necrosis Factor-alpha; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D013853:Thioacetamide; C002669:parthenolide