K20E, an oxidative-coupling compound of methyl caffeate, exhibits anti-angiogenic activities through down-regulations of VEGF and VEGF receptor-2

Chun Hsu Pan, Wen Hsin Lin, Yi Chung Chien, Fon Chang Liu, Ming Jyh Sheu, Yueh Hsiung Kuo, Chieh Hsi Wu

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Anti-angiogenesis is one of the most popular clinical interventions for cancer chemotherapy. A series of synthesized derivative of methyl caffeate were used to evaluate the anti-angiogenic activity and to investigate possible pharmacological mechanisms in the present study. The most potent anti-angiogenic compound was evaluated in the experiments of murine allograft tumor model and Matrigel plug assay as well as cell models in the human umbilical vascular endothelial cells (HUVECs) and the LLC1 lung cancer cells. Our results suggested that K20E suppressed the tumor growth in the allograft tumor model and exhibited anti-angiogenic activity in Matrigel plug assay. Besides, HUVEC viability was found to be significantly reduced by arresting cell cycle at G2/M phase and apoptosis. Cell migration, invasion, and tube formation of the HUVECs were also markedly suppressed by K20E treatment. K20E largely down-regulated the intracellular and secreted vascular endothelial growth factor (VEGF) in the LLC1 cancer cells. Besides, VEGF receptor-2 (VEGFR-2) and its downstream signaling cascades (AKT-mTOR and MEK1/2-ERK1/2) as well as gelatinases were all evidently reduced in the HUVECs treated with K20E. Inversely, K20E can up-regulate the expression levels of p53 and p21 proteins in the HUVECs. Based on these results, our study suggested that K20E possessed inhibiting angiogenesis through regulation of VEGF/VEGFR-2 and its downstream signaling cascades in the vascular endothelial cells (VECs).

Original languageEnglish
Pages (from-to)215-226
Number of pages12
JournalToxicology and Applied Pharmacology
Volume282
Issue number2
DOIs
Publication statusPublished - Jan 5 2015

Fingerprint

Oxidative Coupling
Vascular Endothelial Growth Factor Receptor-2
Endothelial cells
Umbilicus
Vascular Endothelial Growth Factor A
Down-Regulation
Endothelial Cells
Tumors
Cells
Neoplasms
Allografts
Assays
Gelatinases
Vascular Endothelial Growth Factor Receptor
Chemotherapy
G2 Phase
Cell Division
Cell Movement
methyl caffeate
Lung Neoplasms

Keywords

  • Angiogenesis
  • Human umbilical vein endothelial cells
  • K20E
  • Methyl caffeate
  • Vascular endothelial growth factor
  • VEGF receptor-2

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology
  • Medicine(all)

Cite this

K20E, an oxidative-coupling compound of methyl caffeate, exhibits anti-angiogenic activities through down-regulations of VEGF and VEGF receptor-2. / Pan, Chun Hsu; Lin, Wen Hsin; Chien, Yi Chung; Liu, Fon Chang; Sheu, Ming Jyh; Kuo, Yueh Hsiung; Wu, Chieh Hsi.

In: Toxicology and Applied Pharmacology, Vol. 282, No. 2, 05.01.2015, p. 215-226.

Research output: Contribution to journalArticle

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abstract = "Anti-angiogenesis is one of the most popular clinical interventions for cancer chemotherapy. A series of synthesized derivative of methyl caffeate were used to evaluate the anti-angiogenic activity and to investigate possible pharmacological mechanisms in the present study. The most potent anti-angiogenic compound was evaluated in the experiments of murine allograft tumor model and Matrigel plug assay as well as cell models in the human umbilical vascular endothelial cells (HUVECs) and the LLC1 lung cancer cells. Our results suggested that K20E suppressed the tumor growth in the allograft tumor model and exhibited anti-angiogenic activity in Matrigel plug assay. Besides, HUVEC viability was found to be significantly reduced by arresting cell cycle at G2/M phase and apoptosis. Cell migration, invasion, and tube formation of the HUVECs were also markedly suppressed by K20E treatment. K20E largely down-regulated the intracellular and secreted vascular endothelial growth factor (VEGF) in the LLC1 cancer cells. Besides, VEGF receptor-2 (VEGFR-2) and its downstream signaling cascades (AKT-mTOR and MEK1/2-ERK1/2) as well as gelatinases were all evidently reduced in the HUVECs treated with K20E. Inversely, K20E can up-regulate the expression levels of p53 and p21 proteins in the HUVECs. Based on these results, our study suggested that K20E possessed inhibiting angiogenesis through regulation of VEGF/VEGFR-2 and its downstream signaling cascades in the vascular endothelial cells (VECs).",
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AU - Sheu, Ming Jyh

AU - Kuo, Yueh Hsiung

AU - Wu, Chieh Hsi

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