Emodin inhibits TNF-alpha-induced human aortic smooth-muscle cell proliferation via caspase- and mitochondrial-dependent apoptosis.
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-alpha treated human aortic smooth-muscle cells (HASMC). In this study, emodin treatment showed potent inhibitory effects in TNF-alpha-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-alpha 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 (DeltaPsi(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-alpha-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.
Heo
Sook-Kyoung
SK
Cardiovascular Medical Research Center and Department of Prescriptionology University of Dongguk, Gyeongju City, Gyeongbuk 780-714, Republic of Korea.
Yun
Hyun-Jeong
HJ
Park
Won-Hwan
WH
Park
Sun-Dong
SD
D001011:Aorta / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004642:Emodin / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology*; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D019253:Proto-Oncogene Proteins c-bcl-2; D014409:Tumor Necrosis Factor-alpha; D051550:I-kappa B Kinase; D020169:Caspases; D004642:Emodin