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

Research output: Contribution to journalArticle

1 Citation (Scopus)

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.

Original languageEnglish
Pages (from-to)81-89
Number of pages9
JournalMolecular and Cellular Biochemistry
Volume344
Issue number1-2
DOIs
Publication statusPublished - Nov 2010
Externally publishedYes

Fingerprint

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

Keywords

  • Migration
  • OSU-03012
  • Percutaneous transluminal coronary angioplasty (PTCA)
  • Restenosis
  • Vascular smooth muscle cell (VSMC) proliferation

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

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.

In: Molecular and Cellular Biochemistry, Vol. 344, No. 1-2, 11.2010, p. 81-89.

Research output: Contribution to journalArticle

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. In: Molecular and Cellular Biochemistry. 2010 ; Vol. 344, No. 1-2. pp. 81-89.
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AU - Liu, Wei Hung

AU - Wen, Cheng Hao

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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.

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