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
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 t...
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doaj-9574e832182941cda812b854cce9abf72020-11-24T20:58:50ZengMDPI AGMolecules1420-30492015-05-012058198821210.3390/molecules20058198molecules20058198Antiproliferative 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 CellsPo-Sheng Yang0Meng-Jiy Wang1Thanasekaran Jayakumar2Duen-Suey Chou3Ching-Ya Ko4Ming-Jen Hsu5Cheng-Ying Hsieh6Department of Surgery, MacKay Memorial Hospital and Mackay Medical College, No. 92, Sec. 2, Zhongshan N. Rd., Taipei City 10449, TaiwanDepartment of Pharmacology, School of Medicine, Taipei Medical University, 250 Wu-Hsing St., Taipei 110, TaiwanDepartment of Pharmacology, School of Medicine, Taipei Medical University, 250 Wu-Hsing St., Taipei 110, TaiwanDepartment of Pharmacology, School of Medicine, Taipei Medical University, 250 Wu-Hsing St., Taipei 110, TaiwanDepartment of Pharmacology, School of Medicine, Taipei Medical University, 250 Wu-Hsing St., Taipei 110, TaiwanDepartment of Pharmacology, School of Medicine, Taipei Medical University, 250 Wu-Hsing St., Taipei 110, TaiwanDepartment of Pharmacology, School of Medicine, Taipei Medical University, 250 Wu-Hsing St., Taipei 110, TaiwanAbnormal 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.http://www.mdpi.com/1420-3049/20/5/8198VSMChinokitiolJNK1/2PLC-γ1PCNAG0/G1 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Po-Sheng Yang Meng-Jiy Wang Thanasekaran Jayakumar Duen-Suey Chou Ching-Ya Ko Ming-Jen Hsu Cheng-Ying Hsieh |
spellingShingle |
Po-Sheng Yang Meng-Jiy Wang Thanasekaran Jayakumar Duen-Suey Chou Ching-Ya Ko Ming-Jen Hsu Cheng-Ying Hsieh 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 Molecules VSMC hinokitiol JNK1/2 PLC-γ1 PCNA G0/G1 |
author_facet |
Po-Sheng Yang Meng-Jiy Wang Thanasekaran Jayakumar Duen-Suey Chou Ching-Ya Ko Ming-Jen Hsu Cheng-Ying Hsieh |
author_sort |
Po-Sheng Yang |
title |
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 |
title_short |
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 |
title_full |
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 |
title_fullStr |
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 |
title_full_unstemmed |
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 |
title_sort |
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 |
publisher |
MDPI AG |
series |
Molecules |
issn |
1420-3049 |
publishDate |
2015-05-01 |
description |
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. |
topic |
VSMC hinokitiol JNK1/2 PLC-γ1 PCNA G0/G1 |
url |
http://www.mdpi.com/1420-3049/20/5/8198 |
work_keys_str_mv |
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