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.
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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)
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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
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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)
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