YC-1 [3-(5′-hydroxymethyl-2′-furyl)-1-benzyl indazole] inhibits endothelial cell functions induced by angiogenic factors in vitro and angiogenesis in vivo models

Shiow Lin Pan, Jih Hwa Guh, Chieh Yu Peng, Shih Wei Wang, Ya Ling Chang, Fong Chi Cheng, Jau Hsiang Chang, Sheng Chu Kuo, Fang Yu Lee, Che Ming Teng

Research output: Contribution to journalArticle

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Abstract

Angiogenesis is a process that involves endothelial cell proliferation, migration, invasion, and tube formation, and inhibition of these processes has implications for angiogenesis-mediated disorders. The purpose of this study was to evaluate the antiangiogenic efficacy of YC-1 [3-(5′-hydroxymethyl- 2′-furyl)-1-benzyl indazole] in well characterized in vitro and in vivo systems. YC-1 inhibited the ability of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in a dose-dependent manner to induce proliferation, migration, and tube formation in human umbilical vascular endothelial cells; these outcomes were evaluated using [3H]thymidine incorporation, transwell chamber, and Matrigel-coated slide assays, respectively. YC-1 inhibited VEGF- and bFGF-induced p42/p44 mitogen-activated protein kinase and Akt phosphorylation as well as protein kinase Cα translocation using Western blot analysis. The effect of YC-1 on angiogenesis in vivo was evaluated using the mouse Matrigel implant model. YC-1 administered orally in doses of 1 to 100 mg/kg/day inhibited VEGF- and bFGF-induced neovascularization in a dose-dependent manner over 7 days. These results indicate that YC-1 has antiangiogenic activity at very low doses. Moreover, in transplantable murine tumor models, YC-1 administered orally displayed a high degree of antitumor activity (treatment-to-control life span ratio > 175%) without cytotoxicity. YC-1 may be useful for treating angiogenesis-dependent human diseases such as cancer.

Original languageEnglish
Pages (from-to)35-42
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume314
Issue number1
DOIs
Publication statusPublished - Jul 2005
Externally publishedYes

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Indazoles
Angiogenesis Inducing Agents
Fibroblast Growth Factor 2
Vascular Endothelial Growth Factor A
Endothelial Cells
Umbilicus
Mitogen-Activated Protein Kinase 1
Thymidine
Protein Kinase C
Cell Movement
Neoplasms
Western Blotting
Phosphorylation
Cell Proliferation
In Vitro Techniques
matrigel

ASJC Scopus subject areas

  • Pharmacology

Cite this

YC-1 [3-(5′-hydroxymethyl-2′-furyl)-1-benzyl indazole] inhibits endothelial cell functions induced by angiogenic factors in vitro and angiogenesis in vivo models. / Pan, Shiow Lin; Guh, Jih Hwa; Peng, Chieh Yu; Wang, Shih Wei; Chang, Ya Ling; Cheng, Fong Chi; Chang, Jau Hsiang; Kuo, Sheng Chu; Lee, Fang Yu; Teng, Che Ming.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 314, No. 1, 07.2005, p. 35-42.

Research output: Contribution to journalArticle

Pan, Shiow Lin ; Guh, Jih Hwa ; Peng, Chieh Yu ; Wang, Shih Wei ; Chang, Ya Ling ; Cheng, Fong Chi ; Chang, Jau Hsiang ; Kuo, Sheng Chu ; Lee, Fang Yu ; Teng, Che Ming. / YC-1 [3-(5′-hydroxymethyl-2′-furyl)-1-benzyl indazole] inhibits endothelial cell functions induced by angiogenic factors in vitro and angiogenesis in vivo models. In: Journal of Pharmacology and Experimental Therapeutics. 2005 ; Vol. 314, No. 1. pp. 35-42.
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abstract = "Angiogenesis is a process that involves endothelial cell proliferation, migration, invasion, and tube formation, and inhibition of these processes has implications for angiogenesis-mediated disorders. The purpose of this study was to evaluate the antiangiogenic efficacy of YC-1 [3-(5′-hydroxymethyl- 2′-furyl)-1-benzyl indazole] in well characterized in vitro and in vivo systems. YC-1 inhibited the ability of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in a dose-dependent manner to induce proliferation, migration, and tube formation in human umbilical vascular endothelial cells; these outcomes were evaluated using [3H]thymidine incorporation, transwell chamber, and Matrigel-coated slide assays, respectively. YC-1 inhibited VEGF- and bFGF-induced p42/p44 mitogen-activated protein kinase and Akt phosphorylation as well as protein kinase Cα translocation using Western blot analysis. The effect of YC-1 on angiogenesis in vivo was evaluated using the mouse Matrigel implant model. YC-1 administered orally in doses of 1 to 100 mg/kg/day inhibited VEGF- and bFGF-induced neovascularization in a dose-dependent manner over 7 days. These results indicate that YC-1 has antiangiogenic activity at very low doses. Moreover, in transplantable murine tumor models, YC-1 administered orally displayed a high degree of antitumor activity (treatment-to-control life span ratio > 175{\%}) without cytotoxicity. YC-1 may be useful for treating angiogenesis-dependent human diseases such as cancer.",
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AU - Guh, Jih Hwa

AU - Peng, Chieh Yu

AU - Wang, Shih Wei

AU - Chang, Ya Ling

AU - Cheng, Fong Chi

AU - Chang, Jau Hsiang

AU - Kuo, Sheng Chu

AU - Lee, Fang Yu

AU - Teng, Che Ming

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AB - Angiogenesis is a process that involves endothelial cell proliferation, migration, invasion, and tube formation, and inhibition of these processes has implications for angiogenesis-mediated disorders. The purpose of this study was to evaluate the antiangiogenic efficacy of YC-1 [3-(5′-hydroxymethyl- 2′-furyl)-1-benzyl indazole] in well characterized in vitro and in vivo systems. YC-1 inhibited the ability of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in a dose-dependent manner to induce proliferation, migration, and tube formation in human umbilical vascular endothelial cells; these outcomes were evaluated using [3H]thymidine incorporation, transwell chamber, and Matrigel-coated slide assays, respectively. YC-1 inhibited VEGF- and bFGF-induced p42/p44 mitogen-activated protein kinase and Akt phosphorylation as well as protein kinase Cα translocation using Western blot analysis. The effect of YC-1 on angiogenesis in vivo was evaluated using the mouse Matrigel implant model. YC-1 administered orally in doses of 1 to 100 mg/kg/day inhibited VEGF- and bFGF-induced neovascularization in a dose-dependent manner over 7 days. These results indicate that YC-1 has antiangiogenic activity at very low doses. Moreover, in transplantable murine tumor models, YC-1 administered orally displayed a high degree of antitumor activity (treatment-to-control life span ratio > 175%) without cytotoxicity. YC-1 may be useful for treating angiogenesis-dependent human diseases such as cancer.

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