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Tanshinone II A Induces Apoptosis and S Phase Cell Cycle Arrest in Activated Rat Hepatic Stellate Cells
Author(s) -
Che XianHua,
Park EunJeon,
Zhao YuZhe,
Kim WoongHyun,
Sohn Dong Hwan
Publication year - 2010
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/j.1742-7843.2009.00465.x
Subject(s) - salvia miltiorrhiza , hepatic stellate cell , apoptosis , cell cycle checkpoint , cell cycle , hepatic fibrosis , dna fragmentation , chemistry , microbiology and biotechnology , viability assay , pharmacology , cancer research , programmed cell death , biology , fibrosis , medicine , biochemistry , pathology , traditional chinese medicine , endocrinology , alternative medicine
Tanshinone IIA, a major component extracted from the traditional herbal medicine, Salvia miltiorrhiza Bunge, improves blood circulation and treats chronic hepatitis and hepatic fibrosis. Activation of hepatic stellate cells (HSCs) is the predominant event in liver fibrosis. The therapeutic goal in liver fibrosis is the reversal of fibrosis and selective clearance of activated HSCs. We used rat HSCs transformed by Simian virus 40 (t‐HSC/Cl‐6) to overcome the limitations inherent in studying subcultures of HSCs. Treatment of t‐HSC/Cl‐6 cells with tanshinone IIA inhibited cell viability in a dose‐ and time‐dependent manner. Tanshinone IIA induced apoptosis as demonstrated by DNA fragmentation, poly(ADP‐ribose) polymerase and caspase‐3 cleavage, increased Bax/Bcl‐2 protein ratio, and depolarization of mitochondrial membranes to facilitate cytochrome c release into the cytosol. Furthermore, this compound markedly induced S phase cell cycle arrest, and down‐regulated cyclins A and E, and cdk2. Thus, tanshinone IIA induces apoptosis and S phase cell cycle arrest in rat HSCs in vitro .