title: Shikonin inhibits TNF-α-induced growth and invasion of rat aortic vascular smooth muscle cells.
abstract: Shikonin is a naphthoquinone compound extracted from the Chinese herb purple gromwell. Shikonin has broad antibacterial, anti-inflammatory, and antitumor activities. The tumor necrosis factor-α (TNF-α)-induced proliferation and invasion of vascular smooth muscle cells (VSMCs) is an important factor that contributes to atherosclerosis. The effects of shikonin on the proliferation and apoptosis of VSMCs have been reported; however, the function of shikonin on TNF-α-mediated growth and invasion of VSMCs during atherosclerosis remains unclear. In this study, we used Western blot, flow cytometry, real-time quantitative PCR, and enzyme-linked immunosorbent assay to investigate the effect of shikonin on the TNF-α-induced growth and invasion of VSMCs and to determine the underlying mechanism. Our results showed that shikonin inhibits the TNF-α-mediated growth and invasion. Further study revealed that shikonin regulates the activation of nuclear factor kappa B and phosphatidyl inositol 3-kinase signaling pathways; modulates the expression of cyclin D1, cyclin E, B-cell lymphoma 2, and Bax; activates caspase-3 and caspase-9; induces cell cycle arrest; and promotes the apoptosis of VSMCs. Together, our results indicate that shikonin may become a promising agent for the treatment of atherosclerosis and they also establish foundation for the development of anti-atherosclerosis drugs.
authors.affiliation: a Department of Cardiology, The First Affiliated Hospital of China Medical University, 155 North Nanjing Street, Shenyang 110001, People's Republic of China.
authors.forename: Xuemin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: a Department of Cardiology, The First Affiliated Hospital of China Medical University, 155 North Nanjing Street, Shenyang 110001, People's Republic of China.
authors.forename: Wenyu
authors.initials: W
authors.lastname: Hu
authors.affiliation: b Department of Cardiology, The First People's Hospital of Shenyang City, Shenyang 110041, People's Republic of China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wu
authors.affiliation: b Department of Cardiology, The First People's Hospital of Shenyang City, Shenyang 110041, People's Republic of China.
authors.forename: Xue
authors.initials: X
authors.lastname: Yuan
authors.affiliation: a Department of Cardiology, The First Affiliated Hospital of China Medical University, 155 North Nanjing Street, Shenyang 110001, People's Republic of China.
authors.forename: Jian
authors.initials: J
authors.lastname: Hu
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D017209:Apoptosis / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects* / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects* / Q000235:genetics; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009285:Naphthoquinones / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D000893:Anti-Inflammatory Agents; D009285:Naphthoquinones; D014409:Tumor Necrosis Factor-alpha; C016101:shikonin
keywords: NF-κB; PI3K; TNF-α; apoptose; apoptosis; infiltration; invasion; proliferation; prolifération; shikonin; shikonine