Murrayafoline A Induces a G0/G1-Phase Arrest in Platelet-Derived Growth Factor-Stimulated Vascular Smooth Muscle Cells.
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.
Department of Pharmacology, Chungnam National University College of Pharmacy, Daejeon 305-764, Korea.
Joo-Hui
JH
Han
Department of Pharmacology, Chungnam National University College of Pharmacy, Daejeon 305-764, Korea.
Yohan
Y
Kim
Department of Pharmacology, Chungnam National University College of Pharmacy, Daejeon 305-764, Korea.
Sang-Hyuk
SH
Jung
KM Application Center, Korea Institute of Oriental Medicine, Daegu 701-300, Korea.
Jung-Jin
JJ
Lee
Department of Pharmacology, Chungnam National University College of Pharmacy, Daejeon 305-764, Korea.
Hyun-Soo
HS
Park
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.
Gyu-Yong
GY
Song
Institute of Natural Products Chemistry, Vietnam Academy of Science and Technology (VAST), 18 Hoang Quoc Viet St., 122100 Caugiay, Hanoi, Vietnam.
Nguyen Manh
NM
Cuong
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.
Young Ho
YH
Kim
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.
Chang-Seon
CS
Myung
Cell cycle; Murrayafoline A; Platelet-derived growth factor; Proliferation; Vascular smooth muscle cells