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Enterostatin inhibition of angiogenesis: possible role of pAMPK and vascular endothelial growth factor A (VEGF-A)

International Journal of Obesity volume 32, pages 922–929 (2008)Cite this article

Abstract

Introduction:

We utilized a genomic analysis of the response of neuronal GT1-7 cells to enterostatin to identify pathways responsive to this peptide. This information, together with reported properties of the enterostatin receptor, suggested that enterostatin may have an effect on angiogenesis.

Method:

To investigate this hypothesis, we studied the effect of enterostatin as an antiangiogenic agent in two angiogenic tissue culture model systems.

Results:

Enterostatin induced a 50% or greater inhibition in the angiogenic response of human fat cells and had a U-shaped bimodal dose–response effect in inhibiting angiogenesis in a human placental vein angiogenesis model. To further understand this response, we tested enterostatin's effect in a human hepatoma cell line (HepG2 cells) that was subjected to glucose deprivation, a condition known to induce angiogenesis in other tumor cell lines. Phosphorylated AMP kinase (pAMPK) levels and vascular endothelial growth factor A (VEGF-A) mRNA expression were elevated robustly after incubation of HepG2 cells in the absence of glucose for 4 h, but 15 min incubation with enterostatin dramatically inhibited this pAMPK activation and reduced VEGF-A gene expression after 1 h incubation with enterostatin. The AMPK activator 5-aminoimidazole-4-carboximide ribonucleoside (AICAR) induced VEGF-A expression.

Summary:

These data suggest that enterostatin has an antiangiogenic effect and suggest that it regulates VEGF-A gene expression through inhibition of AMPK activity.

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Acknowledgements

This study was supported by funding from NIDDK 45278 and from the Utah Science, Technology and Research (USTAR) initiative to DAY.

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Authors and Affiliations

  1. Center for Advanced Nutrition, Utah State University, Logan, UT, USA

    M Park, H Oh & D A York

  2. Department of Surgery, Louisiana State University Health Sciences Center, New Orleans, LA, USA

    J Lyons III & E A Woltering

  3. Pennington Biomedical Research Center, LSU System, Baton Rouge, LA, USA

    Y Yu & F Greenway

Authors
  1. M Park
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  2. J Lyons III
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  3. H Oh
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  4. Y Yu
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  5. E A Woltering
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  6. F Greenway
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  7. D A York
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Correspondence to D A York.

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Park, M., Lyons, J., Oh, H. et al. Enterostatin inhibition of angiogenesis: possible role of pAMPK and vascular endothelial growth factor A (VEGF-A). Int J Obes 32, 922–929 (2008). https://doi.org/10.1038/ijo.2008.16

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  • DOI: https://doi.org/10.1038/ijo.2008.16

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