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KMID : 0811720150190050421
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Korean Journal of Physiology & Pharmacology
2015 Volume.19 No. 5 p.421 ~ p.426
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Murrayafoline A Induces a G0/G1-Phase Arrest in Platelet-Derived Growth Factor-Stimulated Vascular Smooth Muscle Cells
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Han Joo-Hui
Kim Yo-Han
Jung Sang-Hyuk
Lee Jung-Jin
Park Hyun-Soo
Song Gyu-Yong
Cuong Nguyen-Manh
Kim Young-Ho
Myung Chang-Seon
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Abstract
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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 plate-let-derived growth factor (PDGF) is believed to play a central role in the etiology of these pathophy-siological 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 pro-gression through G0/G1 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 G0/G1 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.
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KEYWORD
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Murrayafoline A, Platelet-derived growth factor, Proliferation, Vascular smooth muscle cells, Cell cycle
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