Parthenolide-induced apoptosis of hepatic stellate cells and anti-fibrotic effects in an in vivo rat model.

Experimental & Molecular Medicine
In Hee KimWoo Hyun Park

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 fi...Continue Reading

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Citations

Dec 7, 2013·Environmental Toxicology and Pharmacology·Dong Yeok ShinYung Hyun Choi
May 22, 2013·Drug Discovery Today·Akram GhantousNadine Darwiche
Apr 16, 2013·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Cheng-Yun JinYung Hyun Choi
Jan 7, 2014·Journal of Experimental & Clinical Cancer Research : CR·Xiaofei ZhaoLing Su
Jul 12, 2014·Oxidative Medicine and Cellular Longevity·Jiying JiangXin Wang
Apr 22, 2016·Biotechnology Letters·Sridharan JeyamohanAntony Joseph Velanganni Arockiam
Dec 4, 2013·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Hyun Soo ParkYung Hyun Choi
Aug 1, 2016·European Journal of Pharmacology·Tanaporn KhamphayaJittima Weerachayaphorn
May 31, 2017·Immunopharmacology and Immunotoxicology·Majid BahabadiIraj Khodadadi
Oct 2, 2012·The Journal of Pathology·Carol M Artlett
Jun 22, 2017·Future Medicinal Chemistry·Iman W AchkarShahab Uddin
Sep 19, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Hong ZhuCheng Huang
Sep 28, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Wamidh H Talib, Lina T Al Kury

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