The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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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)
  • Received : 2015.02.19
  • Accepted : 2015.07.24
  • Published : 2015.09.01
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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.

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References

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