Journal
EXPERIMENTAL AND MOLECULAR MEDICINE
Volume 44, Issue 7, Pages 448-456Publisher
NATURE PUBLISHING GROUP
DOI: 10.3858/emm.2012.44.7.051
Keywords
apoptosis; hepatic stellate cells; liver cirrhosis; parthenolide; reactive oxygen species; thioacetamide
Funding
- Basic Science Research Program through the National Research Foundation of Korea
- Ministry of Education, Science and Technology [2011-0009814]
- National R&D Program for Cancer Control [0620220]
- Korean Health Technology R&D Project, Ministry for Health, Welfare and Family affairs, Republic of Korea [A101834]
- Fund of Chonbuk National University Hospital Research Institute of Clinical Medicine
- Korea Health Promotion Institute [A101834] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
- National Research Foundation of Korea [2011-0009814] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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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-kappa B 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-alpha-stimulated NF-kappa B 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.
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