Emodin inhibits TNF-α-induced human aortic smooth-muscle cell proliferation via caspase- and mitochondrial-dependent apoptosis

✍ Scribed by Sook-Kyoung Heo; Hyun-Jeong Yun; Won-Hwan Park; Sun-Dong Park

• Publisher: John Wiley and Sons
• Year: 2008
• Tongue: English
• Weight: 403 KB
• Volume: 105
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/jcb.21805

✦ Synopsis

Abstract

Vascular smooth‐muscle cell (VSMC) proliferation plays a vital role in hypertension, atherosclerosis and restenosis. It has been reported that emodin, an active component extracted from rhubarb, can stop the growth of cancer cells; however, it is not known if emodin exerts similar anti‐atherogenic effects in TNF‐α treated human aortic smooth‐muscle cells (HASMC). In this study, emodin treatment showed potent inhibitory effects in TNF‐α‐induced HASMC proliferation that were associated with induced apoptosis, including the cleavage of poly ADP‐ribose polymerase (PARP). Moreover, inhibitors of caspase‐3, ‐8 and ‐9 (Ac‐DEVD‐CHO, Z‐IETD‐FMK and Z‐LEHD‐FMK) efficiently blocked emodin‐induced apoptosis in TNF‐α treated HASMC. Therefore, emodin‐induced cell death occurred via caspase‐dependent apoptosis. Emodin treatment resulted in the release of cytochrome c into cytosol and a loss of mitochondrial membrane potential (ΔΨ~m~), as well as a decrease in the expression of an anti‐apoptotic protein (Bcl‐2) and an increase in the expression of an a pro‐apoptotic protein (Bax). Emodin‐mediated apoptosis was also blocked by a mitochondrial membrane depolarization inhibitor, which indicates that emodin‐induced apoptosis occurred via a mitochondrial pathway. Taken together, the results of this study showed that emodin inhibits TNF‐α‐induced HASMC proliferation via caspase‐ and a mitochondrial‐dependent apoptotic pathway. In addition, these results indicate that emodin has potential as an anti‐atherosclerosis agent. J. Cell. Biochem. 105: 70–80, 2008. © 2008 Wiley‐Liss, Inc.