Antiproliferative activity of hinokitiol, a tropolone derivative, is mediated via the inductions of p-JNK and p-PLCγ1 signaling in PDGF-BB-Stimulated vascular smooth muscle cells

Po Sheng Yang, Meng Jiy Wang, Thanasekaran Jayakumar, Duen Suey Chou, Ching Ya Ko, Ming Jen Hsu, Cheng Ying Hsieh

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Abnormal proliferation of vascular smooth muscle cells (VSMCs) is important in the pathogenesis of vascular disorders such as atherosclerosis and restenosis. Hinokitiol, a tropolone derivative found in Chamacyparis taiwanensis, has been found to exhibit anticancer activity in a variety of cancers through inhibition of cell proliferation. In the present study, the possible anti-proliferative effect of hinokitiol was investigated on VSMCs. Our results showed that hinokitiol significantly attenuated the PDGF-BB-stimulated proliferation of VSMCs without cytotoxicity. Hinokitiol suppressed the expression of proliferating cell nuclear antigen (PCNA), a maker for cell cycle arrest, and caused G0/G1 phase arrest in cell cycle progression. To investigate the mechanism underlying the anti-proliferative effect of hinokitiol, we examined the effects of hinokitiol on phosphorylations of Akt, ERK1/2, p38 and JNK1/2. Phospholipase C (PLC)-γ1 phosphorylation, its phosphorylated substrates and p27kip1 expression was also analyzed. Pre-treatment of VSMCs with hinikitiol was found to significantly inhibit the PDGF-BB-induced phosphorylations of JNK1/2 and PLC-γ1, however no effects on Akt, ERK1/2, and p38. The up-regulation of p27kip1 was also observed in hinokitiol-treated VSMCs. Taken together, our results suggest that hinokitiol inhibits PDGF-BB-induced proliferation of VSMCs by inducing cell cycle arrest, suppressing JNK1/2 phosphorylation and PLC-γ1, and stimulating p27kip1 expression. These findings suggest that hinokitiol may be beneficial for the treatment of vascular-related disorders and diseases.

Original languageEnglish
Pages (from-to)8198-8212
Number of pages15
JournalMolecules
Volume20
Issue number5
DOIs
Publication statusPublished - May 1 2015

Keywords

  • G0/G1
  • Hinokitiol
  • JNK1/2
  • PCNA
  • PLC-γ1
  • VSMC

ASJC Scopus subject areas

  • Organic Chemistry

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