Pterostilbene, a natural dimethylated analog of resveratrol, inhibits rat aortic vascular smooth muscle cell proliferation by blocking Akt-dependent pathway.

Abstract

Vascular smooth muscle cells (VSMCs) are the main cellular component in the arterial wall, and abnormal proliferation of VSMCs plays a central role in the pathogenesis of atherosclerosis and restenosis after angioplasty, and possibly in the development of hypertension. Pterostilbene, a natural dimethylated analog of resveratrol, is known to have diverse pharmacological activities including anti-cancer, anti-inflammation and anti-oxidant activities. The present study was designed to investigate the effects of pterostilbene on platelet-derived growth factor (PDGF)-BB-induced VSMCs proliferation as well as the molecular mechanisms of the antiproliferative effects. The cell growth of VSMCs was determined by cell counting and [(3)H]thymidine incorporation assays. Pterostilbene significantly inhibited the DNA synthesis and proliferation of PDGF-BB-stimulated VSMCs in a concentration-dependent manner. The inhibition percentages of pterostilbene at 1, 3 and 5microM to VSMCs proliferation were 68.5, 80.7 and 94.6%, respectively. The DNA synthesis of pterostilbene at 1, 3 and 5microM in VSMCs was inhibited by 47.4, 76.7 and 100%, respectively. Pterostilbene inhibited the PDGF-BB-stimulated phosphorylation of Akt kinase. However, pterostilbene did not change the expression of extracellular signal-related kinase (ERK) 1/2, PLCgamma1, phosphatidylinositol (PI)3 kinase and PDGF-Rbeta phosphorylation. In addition, pterostilbene down-regulated the cell cycle-related proteins including the expression of cyclin-dependent kinase (CDK) 2, cyclin E, CDK4, cyclin D1, retinoblastoma (Rb) proteins and proliferative cell nuclear antigen (PCNA). These findings suggest that the inhibition of pterostilbene to the cell proliferation and DNA synthesis of PDGF-BB-stimulated VSMCs may be mediated by the suppression of Akt kinase. Furthermore, pterostilbene may be a potential anti-proliferative agent for the treatment of atherosclerosis and angioplasty restenosis.

• Authors: Eun-Seok Park, Yong Lim, Jin-Tae Hong, Hwan-Soo Yoo, Chong-Kil Lee, Myoung-Yun Pyo, Yeo-Pyo Yun
• Journal: Vascular pharmacology (Vascul Pharmacol) 2010 Jul-Aug Vol. 53 Issue 1-2 Pg. 61-7 ISSN: 1879-3649 [Electronic] United States
• PMID: 20398797 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2010 Elsevier Inc. All rights reserved.

Chemical References

• Platelet-Derived Growth Factor
• Proto-Oncogene Proteins c-sis
• Stilbenes
• Becaplermin
• pterostilbene
• DNA
• Proto-Oncogene Proteins c-akt

Topics

• Animals
• Aorta (drug effects, metabolism)
• Becaplermin
• Cell Proliferation (drug effects)
• Cells, Cultured
• DNA (biosynthesis, drug effects)
• Dose-Response Relationship, Drug
• Muscle, Smooth, Vascular (drug effects, metabolism)
• Myocytes, Smooth Muscle (drug effects, metabolism)
• Phosphorylation (drug effects)
• Platelet-Derived Growth Factor (pharmacology)
• Proto-Oncogene Proteins c-akt (drug effects, metabolism)
• Proto-Oncogene Proteins c-sis
• Rats
• Stilbenes (administration & dosage, pharmacology)