Journal of Pharmacological Sciences (Jan 2012)

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

  • Kyu-Dong Yoo,
  • Eun-Seok Park,
  • Yong Lim,
  • Shin-Il Kang,
  • Su-Hyang Yoo,
  • Ha-Hee Won,
  • Young-Hee Kim,
  • Ick-Dong Yoo,
  • Hwan-Soo Yoo,
  • Jin Tae Hong,
  • Yeo-Pyo Yun

Journal volume & issue
Vol. 118, no. 2
pp. 171 – 177

Abstract

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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. Keywords:: clitocybin A, vascular smooth muscle cell, platelet-derived growth factor (PDGF)-BB, PI3K/Akt pathway