Murrayafoline A Induces a G0/G1-Phase Arrest in Platelet-Derived Growth Factor-Stimulated Vascular Smooth Muscle Cells.
10.4196/kjpp.2015.19.5.421
- Author:
Joo Hui HAN
1
;
Yohan KIM
;
Sang Hyuk JUNG
;
Jung Jin LEE
;
Hyun Soo PARK
;
Gyu Yong SONG
;
Nguyen Manh CUONG
;
Young Ho KIM
;
Chang Seon MYUNG
Author Information
1. Department of Pharmacology, Chungnam National University College of Pharmacy, Daejeon 305-764, Korea. cm8r@cnu.ac.kr
- Publication Type:Original Article
- Keywords:
Murrayafoline A;
Platelet-derived growth factor;
Proliferation;
Vascular smooth muscle cells;
Cell cycle
- MeSH:
Angioplasty, Balloon, Coronary;
Atherosclerosis;
Cell Count;
Cell Cycle;
Cyclin D1;
Cyclin E;
Cyclins;
Down-Regulation;
Muscle, Smooth, Vascular*;
Phosphorylation;
Phosphotransferases;
Platelet-Derived Growth Factor;
Proliferating Cell Nuclear Antigen;
Retinoblastoma Protein;
Rutaceae;
S Phase
- From:The Korean Journal of Physiology and Pharmacology
2015;19(5):421-426
- CountryRepublic of Korea
- Language:English
-
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 [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.
