title: 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.affiliation: College of Pharmacy, CBITRC, Chungbuk National University, Cheongju, Republic of Korea.
authors.forename: Kyu-Dong
authors.initials: KD
authors.lastname: Yoo
authors.forename: Eun-Seok
authors.initials: ES
authors.lastname: Park
authors.forename: Yong
authors.initials: Y
authors.lastname: Lim
authors.forename: Shin-Il
authors.initials: SI
authors.lastname: Kang
authors.forename: Su-Hyang
authors.initials: SH
authors.lastname: Yoo
authors.forename: Ha-Hee
authors.initials: HH
authors.lastname: Won
authors.forename: Hee-Pom
authors.initials: HP
authors.lastname: Lee
authors.forename: Young-Hee
authors.initials: YH
authors.lastname: Kim
authors.forename: Ick-Dong
authors.initials: ID
authors.lastname: Yoo
authors.forename: Hwan-Soo
authors.initials: HS
authors.lastname: Yoo
authors.forename: Jin-Tae
authors.initials: JT
authors.lastname: Hong
authors.forename: Yeo-Pyo
authors.initials: YP
authors.lastname: Yun
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism; D000077214:Becaplermin; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D054833:Isoindoles / Q000494:pharmacology*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism; D051966:Phospholipase C gamma / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D020574:Proto-Oncogene Proteins c-sis / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics
chemical_list: D018797:Cell Cycle Proteins; D054833:Isoindoles; D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin; C546682:clitocybin B; D020797:Receptor, Platelet-Derived Growth Factor beta; D051057:Proto-Oncogene Proteins c-akt; D048052:Mitogen-Activated Protein Kinase 3; D051966:Phospholipase C gamma