title: Clitocybin A, a novel isoindolinone, from the mushroom Clitocybe aurantiaca, inhibits cell proliferation through G1 phase arrest by regulating the PI3K/Akt cascade in vascular smooth muscle cells.
abstract: Abnormal proliferation of vascular smooth muscle cells (VSMCs) plays an essential role in the pathogenesis of vascular diseases, such as atherosclerosis, hypertension, and restenosis. Clitocybin A, a novel isoindolinone, isolated from the culture broth of mushroom Clitocybe aurantiaca has been reported to possess free radical scavenging activity. However, the antiproliferative effects of clitocybin A on VSMCs are unknown. In the present study, we investigated the effect of clitocybin A on platelet-derived growth factor (PDGF)-BB-induced proliferation of VSMCs and examined the molecular basis of the underlying mechanism. Clitocybin A inhibited DNA synthesis and cell proliferation. In accordance with these findings, clitocybin A blocked the PDGF-BB-inducible progression through G0/G1 to S phase of the cell cycle in synchronized cells and decreased the expression of cyclin-dependent kinase (CDK) 2, CDK4, cyclin D1, cyclin E, and proliferative cell nuclear antigen. In addition, clitocybin A inhibited the PDGF-BB-induced phosphorylation of phosphatidylinositol 3 kinase (PI3K) / Akt kinase. However, clitocybin A did not change the expression levels of extracellular signal-related kinase (ERK) 1/2, phospholipase C-γ1, and PDGF-Rβ phosphorylation. These results indicate that clitocybin A may inhibit VSMCs proliferation through G1 phase arrest by regulating the PI3K/Akt pathway.
authors.affiliation: College of Pharmacy, Research Center for Bioresource and Health, Chungbuk National University, 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: 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: D000363:Agaricales / Q000737:chemistry*; D000818:Animals; D000077214:Becaplermin; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D054833:Isoindoles / Q000302:isolation & purification / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D020574:Proto-Oncogene Proteins c-sis / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D054833:Isoindoles; D020574:Proto-Oncogene Proteins c-sis; C535086:clitocybin A; D000077214:Becaplermin; D004247:DNA; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D018844:Cyclin-Dependent Kinases