Tetrandrine induces apoptosis in hepatic stellate cells

• Published in: Phytotherapy research Vol. 18; no. 4; pp. 306 - 309
• Main Authors: Zhao, Yu-Zhe, Kim, Ji-Young, Park, Eun-Jeon, Lee, Sung Hee, Woo, Sun-Wook, Ko, Geonil, Sohn, Dong Hwan
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01.04.2004; Wiley
• Subjects: Alkaloids - administration & dosage; Alkaloids - pharmacology; Alkaloids - therapeutic use; Animals; apoptosis; Apoptosis - drug effects; Benzylisoquinolines - administration & dosage; Benzylisoquinolines - pharmacology; Benzylisoquinolines - therapeutic use; Biological and medical sciences; Caspases - metabolism; Cells, Cultured - drug effects; DNA Fragmentation; Dose-Response Relationship, Drug; Drugs, Chinese Herbal - administration & dosage; Drugs, Chinese Herbal - pharmacology; Drugs, Chinese Herbal - therapeutic use; Flow Cytometry; General pharmacology; hepatic stellate cells; Liver - cytology; Liver - drug effects; Liver - enzymology; Liver Cirrhosis - drug therapy; liver fibrosis; Medical sciences; Pharmacognosy. Homeopathy. Health food; Pharmacology. Drug treatments; Phytotherapy; Poly(ADP-ribose) Polymerases - metabolism; Rats; Rats, Sprague-Dawley; Stephania tetrandra; tetrandrine; Rat; Liver; Calcium antagonist; Papovaviridae; Accumulation; Fragmentation; Alkaloid; hepatic stellate cells; Digestive system; Enzyme; Polyomavirus; Rodentia; Caspase; Simian virus 40; Virus; Peptidases; Vertebrata; liver fibrosis; Mammalia; Treatment; Cell death; Animal; DNA; Content; Fibrosis; Hydrolases; tetrandrine; Apoptosis
• ISSN: 0951-418X; 1099-1573
• DOI: 10.1002/ptr.1435

We have previously reported that tetrandrine reduced hepatic stellate cell activation and collagen accumulation in liver fibrosis induced by biliary obstruction. In the present study, we examined the apoptosis‐inducing effect of tetrandrine on activated hepatic stellate cells, as the therapeutic goal in hepatic fibrosis is to eliminate the activated hepatic stellate cells by apoptosis. We used rat hepatic stellate cells transformed by Simian virus 40 (T‐HSC/Cl‐6) to overcome the limitations inherent in studying primary cultures of hepatic stellate cells. Tetrandrine treatment at doses of 25 and 50 µg/ml for 12 h induced apoptosis as confirmed by DNA fragmentation and increased sub‐G1 DNA content as detected by flow cytometric analysis. Tetrandrine also induced the activation of caspase‐3 protease and subsequent proteolytic cleavage of poly(ADP‐ribose) polymerase. In conclusion, our results demonstrate that tetrandrine induces apoptosis of T‐HSC/Cl‐6 cells, and these results should contribute to the development of new agents for the treatment of hepatic fibrosis. Copyright © 2004 John Wiley & Sons, Ltd.