Explore the Molecular Mechanism of Apoptosis Induced by Tanshinone IIA on Activated Rat.pdf

Hindawi Publishing Corporation Evidence-Based Complementary and Alternative Medicine Volume 2012, Article ID 734987, 15 pages doi:10.1155/2012/734987 Research Article Explore theMolecular Mechanism of Apoptosis Induced by Tanshinone IIA on Activated Rat Hepatic Stellate Cells Tai-Long Pan1, 2 and Pei-WenWang1 1 School of Traditional Chinese Medicine, Chang Gung University, Kweishan, Taoyuan 333, Taiwan 2Chinese Herbal Medicine Research Team, Healthy Aging Research Center, Chang Gung University, Taoyuan 333, Taiwan Correspondence should be addressed to Tai-Long Pan, pan@mail.cgu.edu.tw Received 23 July 2012; Revised 28 November 2012; Accepted 7 December 2012 Academic Editor: Youn Chul Kim Copyright ? 2012 T.-L. Pan and P.-W. Wang. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Since the activated hepatic stellate cell (HSC) is the predominant event in the progression of liver fibrosis, selective clearance of HSC should be a potential strategy in therapy. Salvia miltiorrhiza roots ethanol extract (SMEE) remarkably ameliorates liver fibrogenesis in DMN-administrated rat model. Next, tanshinone IIA (Tan IIA), the major compound of SMEE, significantly inhibited rat HSC viability and led to cell apoptosis. Proteome tools elucidated that increased prohibitin is involved in cell cycle arrest under Tan IIA is the treatment while knockdown of prohibitin could attenuate Tan IIA-induced apoptosis. In addition, Tan IIA mediated translocation of C-Raf which interacted with prohibitin activating MAPK and inhibiting AKT signaling in HSC. MAPK antagonist suppressed ERK phosphorylation which was necessary for Tan IIA-induced expression of Bax and cytochrome c. PD98059 also abolished Tan IIA-modulated cleavage of PARP. Our findings suggested that Tan IIA could contribute to apoptosis of HSC by promoting ERK-Bax-caspase