Exploring the molecular mechanisms of OSU-03012 on vascular smooth muscle cell proliferation

Wei Wen Kuo, Jing Ru Weng, Chih Yang Huang, Chang Hai Tsai, Wei Hung Liu, Cheng Hao Wen, Shih Chang Tsai, Chieh Hsi Wu

研究成果: 雜誌貢獻文章

1 引文 (Scopus)

摘要

Restenosis is resulted from the proliferation and migration of vascular smooth muscle cells (VSMCs) from the arterial media into the intima within the vessel lumen following percutaneous transluminal coronary angioplasty (PTCA). OSU-03012, a synthetic compound (2-amino-N-{4-[5-(2-phenanthrenyl)-3- (trifluoromethyl)-1H-pyrazol-1-yl]-phenyl} acetamide) acting as a PDK-1 inhibitor, is used as an apoptosis-promoting anticancer drug. However, whether OSU-03012 can inhibit VSMC proliferation and migration following PTCA remains unclear. In this study, we used A10 smooth muscle cells cultured in 10% FBS for stimulating proliferation and evaluated the inhibitory effects of OSU-03012 on cell proliferation and migration. The data demonstrated that OSU-03012 dose-dependently inhibited A10 cell proliferation examined by Trypan blue, MTT and morphological alteration assays, and inhibited the levels of proliferation-related proteins, proliferating cell nuclear antigen (PCNA), phosphorylated ERK examined by western blotting. Additionally, 10 μM OSU-03012 also enhanced apoptosis examined using DAPI assay by regulating apoptosis-related proteins. Furthermore, compared with the control group, A10 cells treated with 10 μM OSU-03012 showed a lower number of migrating cells examined by Boyden Chamber assay, and a dose-dependently reduced NFkB-dependent and interferon-stimulated response element (ISRE) promoter luciferase activities, implying the anti-migration and anti-inflammation effects of OSU03012. Taken together, this study provides insights into the pharmacological mechanisms of OSU-03012 in preventing smooth muscle cell proliferation, migration, and inflammation supporting the novel discovery of OSU-03012 as an adjuvant therapy for balloon injury-induced restenosis.

原文英語
頁(從 - 到)81-89
頁數9
期刊Molecular and Cellular Biochemistry
344
發行號1-2
DOIs
出版狀態已發佈 - 十一月 2010
對外發佈Yes

指紋

Cell proliferation
Vascular Smooth Muscle
Smooth Muscle Myocytes
Muscle
Cell Proliferation
antineoplaston A10
Cell Movement
Assays
Coronary Balloon Angioplasty
Apoptosis
Cells
Inflammation
Tunica Media
OSU 03012
Trypan Blue
Balloons
Proliferating Cell Nuclear Antigen
Response Elements
Luciferases
Interferons

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Molecular Biology
  • Cell Biology

引用此文

Exploring the molecular mechanisms of OSU-03012 on vascular smooth muscle cell proliferation. / Kuo, Wei Wen; Weng, Jing Ru; Huang, Chih Yang; Tsai, Chang Hai; Liu, Wei Hung; Wen, Cheng Hao; Tsai, Shih Chang; Wu, Chieh Hsi.

於: Molecular and Cellular Biochemistry, 卷 344, 編號 1-2, 11.2010, p. 81-89.

研究成果: 雜誌貢獻文章

Kuo, Wei Wen ; Weng, Jing Ru ; Huang, Chih Yang ; Tsai, Chang Hai ; Liu, Wei Hung ; Wen, Cheng Hao ; Tsai, Shih Chang ; Wu, Chieh Hsi. / Exploring the molecular mechanisms of OSU-03012 on vascular smooth muscle cell proliferation. 於: Molecular and Cellular Biochemistry. 2010 ; 卷 344, 編號 1-2. 頁 81-89.
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abstract = "Restenosis is resulted from the proliferation and migration of vascular smooth muscle cells (VSMCs) from the arterial media into the intima within the vessel lumen following percutaneous transluminal coronary angioplasty (PTCA). OSU-03012, a synthetic compound (2-amino-N-{4-[5-(2-phenanthrenyl)-3- (trifluoromethyl)-1H-pyrazol-1-yl]-phenyl} acetamide) acting as a PDK-1 inhibitor, is used as an apoptosis-promoting anticancer drug. However, whether OSU-03012 can inhibit VSMC proliferation and migration following PTCA remains unclear. In this study, we used A10 smooth muscle cells cultured in 10{\%} FBS for stimulating proliferation and evaluated the inhibitory effects of OSU-03012 on cell proliferation and migration. The data demonstrated that OSU-03012 dose-dependently inhibited A10 cell proliferation examined by Trypan blue, MTT and morphological alteration assays, and inhibited the levels of proliferation-related proteins, proliferating cell nuclear antigen (PCNA), phosphorylated ERK examined by western blotting. Additionally, 10 μM OSU-03012 also enhanced apoptosis examined using DAPI assay by regulating apoptosis-related proteins. Furthermore, compared with the control group, A10 cells treated with 10 μM OSU-03012 showed a lower number of migrating cells examined by Boyden Chamber assay, and a dose-dependently reduced NFkB-dependent and interferon-stimulated response element (ISRE) promoter luciferase activities, implying the anti-migration and anti-inflammation effects of OSU03012. Taken together, this study provides insights into the pharmacological mechanisms of OSU-03012 in preventing smooth muscle cell proliferation, migration, and inflammation supporting the novel discovery of OSU-03012 as an adjuvant therapy for balloon injury-induced restenosis.",
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T1 - Exploring the molecular mechanisms of OSU-03012 on vascular smooth muscle cell proliferation

AU - Kuo, Wei Wen

AU - Weng, Jing Ru

AU - Huang, Chih Yang

AU - Tsai, Chang Hai

AU - Liu, Wei Hung

AU - Wen, Cheng Hao

AU - Tsai, Shih Chang

AU - Wu, Chieh Hsi

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N2 - Restenosis is resulted from the proliferation and migration of vascular smooth muscle cells (VSMCs) from the arterial media into the intima within the vessel lumen following percutaneous transluminal coronary angioplasty (PTCA). OSU-03012, a synthetic compound (2-amino-N-{4-[5-(2-phenanthrenyl)-3- (trifluoromethyl)-1H-pyrazol-1-yl]-phenyl} acetamide) acting as a PDK-1 inhibitor, is used as an apoptosis-promoting anticancer drug. However, whether OSU-03012 can inhibit VSMC proliferation and migration following PTCA remains unclear. In this study, we used A10 smooth muscle cells cultured in 10% FBS for stimulating proliferation and evaluated the inhibitory effects of OSU-03012 on cell proliferation and migration. The data demonstrated that OSU-03012 dose-dependently inhibited A10 cell proliferation examined by Trypan blue, MTT and morphological alteration assays, and inhibited the levels of proliferation-related proteins, proliferating cell nuclear antigen (PCNA), phosphorylated ERK examined by western blotting. Additionally, 10 μM OSU-03012 also enhanced apoptosis examined using DAPI assay by regulating apoptosis-related proteins. Furthermore, compared with the control group, A10 cells treated with 10 μM OSU-03012 showed a lower number of migrating cells examined by Boyden Chamber assay, and a dose-dependently reduced NFkB-dependent and interferon-stimulated response element (ISRE) promoter luciferase activities, implying the anti-migration and anti-inflammation effects of OSU03012. Taken together, this study provides insights into the pharmacological mechanisms of OSU-03012 in preventing smooth muscle cell proliferation, migration, and inflammation supporting the novel discovery of OSU-03012 as an adjuvant therapy for balloon injury-induced restenosis.

AB - Restenosis is resulted from the proliferation and migration of vascular smooth muscle cells (VSMCs) from the arterial media into the intima within the vessel lumen following percutaneous transluminal coronary angioplasty (PTCA). OSU-03012, a synthetic compound (2-amino-N-{4-[5-(2-phenanthrenyl)-3- (trifluoromethyl)-1H-pyrazol-1-yl]-phenyl} acetamide) acting as a PDK-1 inhibitor, is used as an apoptosis-promoting anticancer drug. However, whether OSU-03012 can inhibit VSMC proliferation and migration following PTCA remains unclear. In this study, we used A10 smooth muscle cells cultured in 10% FBS for stimulating proliferation and evaluated the inhibitory effects of OSU-03012 on cell proliferation and migration. The data demonstrated that OSU-03012 dose-dependently inhibited A10 cell proliferation examined by Trypan blue, MTT and morphological alteration assays, and inhibited the levels of proliferation-related proteins, proliferating cell nuclear antigen (PCNA), phosphorylated ERK examined by western blotting. Additionally, 10 μM OSU-03012 also enhanced apoptosis examined using DAPI assay by regulating apoptosis-related proteins. Furthermore, compared with the control group, A10 cells treated with 10 μM OSU-03012 showed a lower number of migrating cells examined by Boyden Chamber assay, and a dose-dependently reduced NFkB-dependent and interferon-stimulated response element (ISRE) promoter luciferase activities, implying the anti-migration and anti-inflammation effects of OSU03012. Taken together, this study provides insights into the pharmacological mechanisms of OSU-03012 in preventing smooth muscle cell proliferation, migration, and inflammation supporting the novel discovery of OSU-03012 as an adjuvant therapy for balloon injury-induced restenosis.

KW - Migration

KW - OSU-03012

KW - Percutaneous transluminal coronary angioplasty (PTCA)

KW - Restenosis

KW - Vascular smooth muscle cell (VSMC) proliferation

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