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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

Authors 

K D YooE S ParkY LimS I KangS H YooH H WonY H KimIck-Dong YooH S YooJ T HongY P Yun

Publisher 

Japanese Pharmacological Society

Issue Date 

2012

Citation 

Journal of Pharmacological Sciences, vol. 118, no. 2, pp. 171-177

Keywords 

Clitocybin API3K/Akt pathwayPlatelet-derived growth factor (PDGF)-BBVascular smooth muscle cell

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.

ISSN 

1347-8613

Link 

http://dx.doi.org/10.1254/jphs.11159FP

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2017-04-19


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