An inhibitory effect of chrysoeriol on platelet-derived growth factor (PDGF)-induced proliferation and PDGF receptor signaling in human aortic smooth muscle cells.
Platelet-derived growth factor (PDGF)-BB is one of the most potent factors in the development and progression of various vascular disorders such as restenosis and atherosclerosis. Chrysoeriol is a flavonoid with antioxidant and anti-inflammatory activities. In this study, we investigated the effect of chrysoeriol on the proliferation of human aortic smooth muscle cells (HASMC). Chrysoeriol significantly inhibited PDGF (20 ng/mL)-induced migration and [(3)H]-thymidine incorporation into DNA at concentrations of 5 and 10 microM without any cytotoxicity. Chrysoeriol also blocked PDGF-stimulated dissociation of actin filament and inhibited PDGF beta-receptor (Rbeta) phosphorylation in a concentration-dependent manner. As a result, the downstream signal transduction pathways of PDGF-Rbeta, including ERK1/2, p38, and Akt phosphorylation, were also inhibited by chrysoeriol in the same pattern. These findings suggest that in addition to its antioxidant and anti-inflammatory activities, chrysoeriol may be used for the prevention and treatment of vascular diseases and during restenosis after coronary angioplasty.
Cha
Byung-Yoon
BY
Research Institute for Biological Functions, Chubu University, Japan.
Shi
Wen Lei
WL
Yonezawa
Takayuki
T
Teruya
Toshiaki
T
Nagai
Kazuo
K
Woo
Je-Tae
JT
D000199:Actins / Q000378:metabolism; D015153:Blotting, Western; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000187:drug effects; D004591:Electrophoresis, Polyacrylamide Gel; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D047309:Flavones; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D032389:Myocytes, Smooth Muscle / Q000187:drug effects*; D051058:Oncogene Protein v-akt / Q000378:metabolism; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D017479:Receptors, Platelet-Derived Growth Factor / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects*; D013936:Thymidine / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D000199:Actins; D047309:Flavones; D005419:Flavonoids; D010982:Platelet-Derived Growth Factor; D017479:Receptors, Platelet-Derived Growth Factor; D051058:Oncogene Protein v-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C007054:chrysoeriol; D013936:Thymidine