Clitocybin B inhibits rat aortic smooth muscle cell proliferation through suppressing PDGF-Rβ phosphorylation.

Abstract

The increased proliferation of vascular smooth muscle cells (VSMCs) in the arterial wall is a critical pathogenic factor for vascular diseases such as atherosclerosis and restenosis after angioplasty. Clitocybin B was reported to have either a potent free radical scavenging effect or effects that were isolated from the culture broth of mushroom Clitocybe aurantiaca. The present study was designed to investigate the effects of clitocybin B on VSMC proliferation and its possible molecular mechanism. Clitocybin B significantly inhibited the proliferation and the DNA synthesis of PDGF-BB-stimulated VSMCs in a concentration-dependent manner. In agreement with these findings, clitocybin B suppressed the PDGF-BB-induced progression through G0/G1 to S phase of cell cycle. Clitocybin B also down-regulated the expressions of cell cycle-related proteins, including cyclin-dependent kinase (CDK)2, cyclin E, CDK4, cyclin D1, and proliferative cell nuclear antigen in PDGF-BB-stimulated VSMCs. Clitocybin B significantly inhibited the phosphorylation of Akt, extracellular signal-regulated kinase 1/2, and phospholipase C-γ1, in the PDGF-BB signaling pathway. Clitocybin B suppressed the PDGF-Rβ activation in PDGF-BB signaling cascade. These results suggested that the inhibitory effect of clitocybin B on the proliferation of VSMCs may be associated with suppressing PDGF-Rβ phosphorylation. Thus, clitocybin B may be an effective antiproliferative agent for the prevention of atherosclerosis and restenosis.

• Authors: Kyu-Dong Yoo, Eun-Seok Park, Yong Lim, Shin-Il Kang, Su-Hyang Yoo, Ha-Hee Won, Hee-Pom Lee, Young-Hee Kim, Ick-Dong Yoo, Hwan-Soo Yoo, Jin-Tae Hong, Yeo-Pyo Yun
• Journal: Vascular pharmacology (Vascul Pharmacol) 2012 Jan-Feb Vol. 56 Issue 1-2 Pg. 91-7 ISSN: 1879-3649 [Electronic] United States
• PMID: 22166585 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Inc. All rights reserved.

Chemical References

• Cell Cycle Proteins
• Isoindoles
• Proto-Oncogene Proteins c-sis
• Becaplermin
• clitocybin B
• Receptor, Platelet-Derived Growth Factor beta
• Proto-Oncogene Proteins c-akt
• Mitogen-Activated Protein Kinase 3
• Phospholipase C gamma

Topics

• Animals
• Aorta (drug effects, metabolism)
• Becaplermin
• Cell Cycle (drug effects, genetics)
• Cell Cycle Proteins (genetics, metabolism)
• Cell Proliferation (drug effects)
• Cells, Cultured
• Down-Regulation (drug effects, genetics)
• Isoindoles (pharmacology)
• Mitogen-Activated Protein Kinase 3 (metabolism)
• Muscle, Smooth, Vascular (cytology, drug effects, metabolism)
• Myocytes, Smooth Muscle (drug effects, metabolism)
• Phospholipase C gamma (metabolism)
• Phosphorylation (drug effects)
• Proto-Oncogene Proteins c-akt (metabolism)
• Proto-Oncogene Proteins c-sis (metabolism, pharmacology)
• Rats
• Receptor, Platelet-Derived Growth Factor beta (antagonists & inhibitors, metabolism)
• Signal Transduction (drug effects, genetics)