Dihydroaustrasulfone Alcohol Inhibits PDGF-Induced Proliferation and Migration of Human Aortic Smooth Muscle Cells through Inhibition of the Cell Cycle
Dihydroaustrasulfone alcohol is the synthetic precursor of austrasulfone, which is a marine natural product, isolated from the Taiwanese soft coral Cladiella australis. Dihydroaustrasulfone alcohol has anti-inflammatory, neuroprotective, antitumor and anti-atherogenic properties. Although dihydroau...
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| Format: | Article |
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MDPI AG
2015-04-01
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| Series: | Marine Drugs |
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| Online Access: | http://www.mdpi.com/1660-3397/13/4/2390 |
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| author | Yao-Chang Chen Zhi-Hong Wen Yen-Hsien Lee Chu-Lun Chen Han-Chun Hung Chun-Hong Chen Wu-Fu Chen Min-Chien Tsai |
| author_facet | Yao-Chang Chen Zhi-Hong Wen Yen-Hsien Lee Chu-Lun Chen Han-Chun Hung Chun-Hong Chen Wu-Fu Chen Min-Chien Tsai |
| author_sort | Yao-Chang Chen |
| collection | DOAJ |
| description | Dihydroaustrasulfone alcohol is the synthetic precursor of austrasulfone, which is a marine natural product, isolated from the Taiwanese soft coral Cladiella australis. Dihydroaustrasulfone alcohol has anti-inflammatory, neuroprotective, antitumor and anti-atherogenic properties. Although dihydroaustrasulfone alcohol has been shown to inhibit neointima formation, its effect on human vascular smooth muscle cells (VSMCs) has not been elucidated. We examined the effects and the mechanisms of action of dihydroaustrasulfone alcohol on proliferation, migration and phenotypic modulation of human aortic smooth muscle cells (HASMCs). Dihydroaustrasulfone alcohol significantly inhibited proliferation, DNA synthesis and migration of HASMCs, without inducing cell death. Dihydroaustrasulfone alcohol also inhibited platelet-derived growth factor (PDGF)-induced expression of cyclin-dependent kinases (CDK) 2, CDK4, cyclin D1 and cyclin E. In addition, dihydroaustrasulfone alcohol inhibited PDGF-induced phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), whereas it had no effect on the phosphorylation of phosphatidylinositol 3-kinase (PI3K)/(Akt). Moreover, treatment with PD98059, a highly selective ERK inhibitor, blocked PDGF-induced upregulation of cyclin D1 and cyclin E and downregulation of p27kip1. Furthermore, dihydroaustrasulfone alcohol also inhibits VSMC synthetic phenotype formation induced by PDGF. For in vivo studies, dihydroaustrasulfone alcohol decreased smooth muscle cell proliferation in a rat model of restenosis induced by balloon injury. Immunohistochemical staining showed that dihydroaustrasulfone alcohol noticeably decreased the expression of proliferating cell nuclear antigen (PCNA) and altered VSMC phenotype from a synthetic to contractile state. Our findings provide important insights into the mechanisms underlying the vasoprotective actions of dihydroaustrasulfone alcohol and suggest that it may be a useful therapeutic agent for the treatment of vascular occlusive disease. |
| first_indexed | 2024-04-14T04:47:23Z |
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| institution | Directory Open Access Journal |
| issn | 1660-3397 |
| language | English |
| last_indexed | 2024-04-14T04:47:23Z |
| publishDate | 2015-04-01 |
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| series | Marine Drugs |
| spelling | doaj.art-8c804efdbf5146678520f5656965e8b02022-12-22T02:11:25ZengMDPI AGMarine Drugs1660-33972015-04-011342390240610.3390/md13042390md13042390Dihydroaustrasulfone Alcohol Inhibits PDGF-Induced Proliferation and Migration of Human Aortic Smooth Muscle Cells through Inhibition of the Cell CycleYao-Chang Chen0Zhi-Hong Wen1Yen-Hsien Lee2Chu-Lun Chen3Han-Chun Hung4Chun-Hong Chen5Wu-Fu Chen6Min-Chien Tsai7Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Lienhai Road, Kaohsiung 804, TaiwanDepartment of Marine Biotechnology and Resources, National Sun Yat-sen University, Lienhai Road, Kaohsiung 804, TaiwanGraduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, 250 Wuxing Street, Taipei 11042, TaiwanDepartment of Physiology and Biophysics; Graduate Institute of Physiology, National Defense Medical Center, Sec. 6, Minquan E. Road, Taipei 11490, TaiwanDoctoral Degree Program in Marine Biotechnology, National Sun Yat-sen University and Academia Sinica, Kaohsiung 80424, TaiwanDoctoral Degree Program in Marine Biotechnology, National Sun Yat-sen University and Academia Sinica, Kaohsiung 80424, TaiwanDepartment of Neurosurgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, TaiwanDepartment of Physiology and Biophysics; Graduate Institute of Physiology, National Defense Medical Center, Sec. 6, Minquan E. Road, Taipei 11490, TaiwanDihydroaustrasulfone alcohol is the synthetic precursor of austrasulfone, which is a marine natural product, isolated from the Taiwanese soft coral Cladiella australis. Dihydroaustrasulfone alcohol has anti-inflammatory, neuroprotective, antitumor and anti-atherogenic properties. Although dihydroaustrasulfone alcohol has been shown to inhibit neointima formation, its effect on human vascular smooth muscle cells (VSMCs) has not been elucidated. We examined the effects and the mechanisms of action of dihydroaustrasulfone alcohol on proliferation, migration and phenotypic modulation of human aortic smooth muscle cells (HASMCs). Dihydroaustrasulfone alcohol significantly inhibited proliferation, DNA synthesis and migration of HASMCs, without inducing cell death. Dihydroaustrasulfone alcohol also inhibited platelet-derived growth factor (PDGF)-induced expression of cyclin-dependent kinases (CDK) 2, CDK4, cyclin D1 and cyclin E. In addition, dihydroaustrasulfone alcohol inhibited PDGF-induced phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), whereas it had no effect on the phosphorylation of phosphatidylinositol 3-kinase (PI3K)/(Akt). Moreover, treatment with PD98059, a highly selective ERK inhibitor, blocked PDGF-induced upregulation of cyclin D1 and cyclin E and downregulation of p27kip1. Furthermore, dihydroaustrasulfone alcohol also inhibits VSMC synthetic phenotype formation induced by PDGF. For in vivo studies, dihydroaustrasulfone alcohol decreased smooth muscle cell proliferation in a rat model of restenosis induced by balloon injury. Immunohistochemical staining showed that dihydroaustrasulfone alcohol noticeably decreased the expression of proliferating cell nuclear antigen (PCNA) and altered VSMC phenotype from a synthetic to contractile state. Our findings provide important insights into the mechanisms underlying the vasoprotective actions of dihydroaustrasulfone alcohol and suggest that it may be a useful therapeutic agent for the treatment of vascular occlusive disease.http://www.mdpi.com/1660-3397/13/4/2390dihydroaustrasulfone alcoholvascular smooth muscle cellproliferationmigrationphenotypic modulationcell cyclerestenosis |
| spellingShingle | Yao-Chang Chen Zhi-Hong Wen Yen-Hsien Lee Chu-Lun Chen Han-Chun Hung Chun-Hong Chen Wu-Fu Chen Min-Chien Tsai Dihydroaustrasulfone Alcohol Inhibits PDGF-Induced Proliferation and Migration of Human Aortic Smooth Muscle Cells through Inhibition of the Cell Cycle Marine Drugs dihydroaustrasulfone alcohol vascular smooth muscle cell proliferation migration phenotypic modulation cell cycle restenosis |
| title | Dihydroaustrasulfone Alcohol Inhibits PDGF-Induced Proliferation and Migration of Human Aortic Smooth Muscle Cells through Inhibition of the Cell Cycle |
| title_full | Dihydroaustrasulfone Alcohol Inhibits PDGF-Induced Proliferation and Migration of Human Aortic Smooth Muscle Cells through Inhibition of the Cell Cycle |
| title_fullStr | Dihydroaustrasulfone Alcohol Inhibits PDGF-Induced Proliferation and Migration of Human Aortic Smooth Muscle Cells through Inhibition of the Cell Cycle |
| title_full_unstemmed | Dihydroaustrasulfone Alcohol Inhibits PDGF-Induced Proliferation and Migration of Human Aortic Smooth Muscle Cells through Inhibition of the Cell Cycle |
| title_short | Dihydroaustrasulfone Alcohol Inhibits PDGF-Induced Proliferation and Migration of Human Aortic Smooth Muscle Cells through Inhibition of the Cell Cycle |
| title_sort | dihydroaustrasulfone alcohol inhibits pdgf induced proliferation and migration of human aortic smooth muscle cells through inhibition of the cell cycle |
| topic | dihydroaustrasulfone alcohol vascular smooth muscle cell proliferation migration phenotypic modulation cell cycle restenosis |
| url | http://www.mdpi.com/1660-3397/13/4/2390 |
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