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.
J Pharmacol Sci
; 118(2): 171-7, 2012.
Article
en En
| MEDLINE
| ID: mdl-22343364
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-Rß phosphorylation. These results indicate that clitocybin A may inhibit VSMCs proliferation through G1 phase arrest by regulating the PI3K/Akt pathway.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Agaricales
/
Proliferación Celular
/
Isoindoles
/
Músculo Liso Vascular
Límite:
Animals
Idioma:
En
Revista:
J Pharmacol Sci
Asunto de la revista:
FARMACOLOGIA
Año:
2012
Tipo del documento:
Article