Tanshinone II A induces apoptosis and S phase cell cycle arrest in activated rat hepatic stellate cells.
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.
Che
Xian-Hua
XH
Department of Pharmacy, Institute of Pharmaceutical Research and Development, Wonkwang University, Iksan, Jeonbuk, South Korea.
Park
Eun-Jeon
EJ
Zhao
Yu-Zhe
YZ
Kim
Woong-Hyun
WH
Sohn
Dong Hwan
DH
D045784:Abietanes; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D055166:Hepatic Stellate Cells / Q000187:drug effects*; D008930:Mitochondria, Liver / Q000187:drug effects / Q000502:physiology; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology; D010616:Phenanthrenes / Q000494:pharmacology*; D051381:Rats; D016196:S Phase / Q000187:drug effects*
D045784:Abietanes; D010616:Phenanthrenes; C021751:tanshinone; D020928:Mitogen-Activated Protein Kinases; D053148:Caspase 3