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http://dx.doi.org/10.4196/kjpp.2015.19.5.421

Murrayafoline A Induces a G0/G1-Phase Arrest in Platelet-Derived Growth Factor-Stimulated Vascular Smooth Muscle Cells  

Han, Joo-Hui (Department of Pharmacology, Chungnam National University College of Pharmacy)
Kim, Yohan (Department of Pharmacology, Chungnam National University College of Pharmacy)
Jung, Sang-Hyuk (Department of Pharmacology, Chungnam National University College of Pharmacy)
Lee, Jung-Jin (KM Application Center, Korea Institute of Oriental Medicine)
Park, Hyun-Soo (Department of Pharmacology, Chungnam National University College of Pharmacy)
Song, Gyu-Yong (Department of Medicinal Chemistry, Chungnam National University College of Pharmacy)
Nguyen, Manh Cuong (Institute of Natural Products Chemistry, Vietnam Academy of Science and Technology (VAST))
Kim, Young Ho (Institute of Drug Research & Development, Chungnam National University)
Myung, Chang-Seon (Department of Pharmacology, Chungnam National University College of Pharmacy)
Publication Information
The Korean Journal of Physiology and Pharmacology / v.19, no.5, 2015 , pp. 421-426 More about this Journal
Abstract
The increased potential for vascular smooth muscle cell (VSMC) growth is a key abnormality in the development of atherosclerosis and post-angioplasty restenosis. Abnormally high activity of platelet-derived growth factor (PDGF) is believed to play a central role in the etiology of these pathophysiological situations. Here, we investigated the anti-proliferative effects and possible mechanism(s) of murrayafoline A, a carbazole alkaloid isolated from Glycosmis stenocarpa Guillamin (Rutaceae), on PDGF-BB-stimulated VSMCs. Murrayafoline A inhibited the PDGF-BB-stimulated proliferation of VSMCs in a concentration-dependent manner, as measured using a non-radioactive colorimetric WST-1 assay and direct cell counting. Furthermore, murrayafoline A suppressed the PDGF-BB-stimulated progression through $G_0/G_1$ to S phase of the cell cycle, as measured by [$^3H$]-thymidine incorporation assay and cell cycle progression analysis. This anti-proliferative action of murrayafoline A, arresting cell cycle progression at $G_0/G_1$ phase in PDGF-BB-stimulated VSMCs, was mediated via down-regulation of the expression of cyclin D1, cyclin E, cyclin-dependent kinase (CDK)2, CDK4, and proliferating cell nuclear antigen (PCNA), and the phosphorylation of retinoblastoma protein (pRb). These results indicate that murrayafoline A may be useful in preventing the progression of vascular complications such as restenosis after percutaneous transluminal coronary angioplasty and atherosclerosis.
Keywords
Murrayafoline A; Platelet-derived growth factor; Proliferation; Vascular smooth muscle cells; Cell cycle;
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