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

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

  • Korean J Physiol Pharmacol. 2015 Sep;19(5):421-6. doi: 10.4196/kjpp.2015.19.5.421.
Joo-Hui Han 1,  Yohan Kim 1,  Sang-Hyuk Jung 1,  Jung-Jin Lee 2,  Hyun-Soo Park 1,  Gyu-Yong Song 3,  Nguyen Manh Cuong 4,  Young Ho Kim 5,  Chang-Seon Myung 6
Affiliations

Affiliations

  • 1 Department of Pharmacology, Chungnam National University College of Pharmacy, Daejeon 305-764, Korea.
  • 2 KM Application Center, Korea Institute of Oriental Medicine, Daegu 701-300, Korea.
  • 3 Department of Medicinal Chemistry, Chungnam National University College of Pharmacy, Daejeon 305-764, Korea. ; Institute of Drug Research & Development, Chungnam National University, Daejeon 305-764, Korea.
  • 4 Institute of Natural Products Chemistry, Vietnam Academy of Science and Technology (VAST), 18 Hoang Quoc Viet St., 122100 Caugiay, Hanoi, Vietnam.
  • 5 Institute of Drug Research & Development, Chungnam National University, Daejeon 305-764, Korea. ; Department of Natural Product Chemistry, Chungnam National University College of Pharmacy, Daejeon 305-764, Korea.
  • 6 Department of Pharmacology, Chungnam National University College of Pharmacy, Daejeon 305-764, Korea. ; Institute of Drug Research & Development, Chungnam National University, Daejeon 305-764, Korea.
PMID: 26330754 DOI: 10.4196/kjpp.2015.19.5.421
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 G0/G1 to S phase of the cell cycle, as measured by [(3)H]-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.

Keywords

Cell cycle; Murrayafoline A; Platelet-derived growth factor; Proliferation; Vascular smooth muscle cells.

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