title: Gleditsia sinensis thorn extract inhibits the proliferation and migration of PDGF‑induced vascular smooth muscle cells.
abstract: The thorns of Gleditsia sinensis have been used to prevent or treat numerous diseases. The present study aimed to investigate the molecular mechanism of the ethanol extract of Gleditsia sinensis thorns (EEGS) on platelet-derived growth factor (PDGF)‑treated vascular smooth muscle cells (VSMCs). EEGS treatment was found to inhibit DNA synthesis in PDG\F-treated VSMCs in a dose-dependent manner, without cell toxicity. These inhibitory effects were associated with G1-phase cell-cycle arrest, which was caused by the decreased expression of cyclins and cyclin-dependent kinases (CDKs) and the upregulation of p27KIP1 expression in PDGF-stimulated VSMCs. Among the pathways examined, EEGS treatment was observed to only inhibit the PDGF‑induced phosphorylation of Akt. In addition, EEGS treatment suppressed the migration and invasion of VSMCs in the presence of PDGF as determined by wound-healing and Matrigel™ invasion assays. Furthermore, zymographic and western blot analyses revealed that EEGS treatment suppressed matrix metalloproteinase (MMP)-9 expression in PDGF‑treated VSMCs, which was attributed to a reduction in the binding activities of nuclear factor κ-light-chain-enhancer of activated B cells (NF‑κB), activator protein (AP)‑1 and specificity protein (Sp)‑1. These results demonstrate that EEGS induces p27KIP1‑mediated G1-phase cell-cycle arrest, reduces Akt phosphorylation and prevents MMP‑9 expression by decreasing the binding activities of NF‑κB, AP‑1 and Sp‑1 in PDGF-treated VSMCs, thus resulting in growth inhibition and the suppression of migration and invasion. These results may suggest a novel perspective for the use of EEGS in the treatment and prevention of vascular proliferative diseases.
authors: Department of Food Science and Nutrition, Jeju National University, Jeju, Jeju Special Self‑Governing Province 690‑756, Republic of Korea.
authors: Sung-Soo
authors: SS
authors: Park
authors: Department of Urology, Chungbuk National University College of Medicine, Cheongju, Chungbuk 361‑763, Republic of Korea.
authors: Wun-Jae
authors: WJ
authors: Kim
authors: School of Food Science and Technology, Chung‑Ang University, Anseong, Gyeonggi‑Do 456‑756, Republic of Korea.
authors: Sung-Kwon
authors: SK
authors: Moon
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D031501:Gleditsia / Q000737:chemistry* / Q000378:metabolism; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D010936:Plant Extracts / Q000737:chemistry / Q000633:toxicity*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D011485:Protein Binding; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016329:Sp1 Transcription Factor / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism
chemical_list: D016328:NF-kappa B; D010936:Plant Extracts; D010982:Platelet-Derived Growth Factor; D016329:Sp1 Transcription Factor; D018808:Transcription Factor AP-1; D050760:Cyclin-Dependent Kinase Inhibitor p27; D051057:Proto-Oncogene Proteins c-akt; D020780:Matrix Metalloproteinase 9