Anti-angiogenic properties of a sulindac analogue

A. Pyriochou, S. Tsigkos, T. Vassilakopoulos, T. Cottin, Z. Zhou, E. Gourzoulidou, C. Roussos, H. Waldmann, A. Giannis, Andreas Papapetropoulos

Research output: Contribution to journalArticle

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Abstract

Background and purpose: Angiopoietins (Ang) are crucial for new blood vessel formation and exert their effects by acting on the Tie2 receptor. We have recently described a sulindac analogue 2-((1E,Z)-1-benzylidene-5-bromo-2- methyl-1H-inden-3-yl)acetic acid; termed C-18 from now onwards) that inhibits Tie2 receptor activity in kinase assays in vitro. Here, we have assessed the ability of C-18 to inhibit angiogenesis-related properties of endothelial cells and tested its selectivity for the Tie2 receptor. Experimental approach: For in vitro experiments human umbilical vein endothelial cells (HUVEC) were used. Proliferation was measured using the MTT assay; migration assays were performed in a modified Boyden chamber and tube-like structure formation was determined on matrigel. The effects of C-18 in vivo were evaluated in the chicken chorioallantoic membrane (CAM). Key results: Pre-treatment of HUVEC with C-18 blocked Ang-1-stimulated migration, but also abolished vascular endothelial cell growth factor (VEGF)- and fibroblast growth factor 2-induced responses. Incubation with C-18 inhibited serum-induced proliferation in a concentration-dependent manner; C-18 was, however, without effect on Ang-1-induced survival. In addition, we observed that C-18 did not inhibit ligand-induced receptor phosphorylation of Tie2 or VEGFR2. On the other hand, C-18 blocked activation of members of the mitogen-activated protein kinase family and of the Ser/Thr kinase Akt induced by both VEGF and Ang-1. Furthermore, incubation of CAMs with C-18 led to a dose-dependent inhibition of vascular length. Conclusions and implications: C-18 did not act as a Tie2 inhibitor, as originally thought, but rather inhibited growth factor-stimulated signalling pathways that regulate endothelial cell migration and potently reduces neovascularization in vivo.

Original languageEnglish (US)
Pages (from-to)1207-1214
Number of pages8
JournalBritish Journal of Pharmacology
Volume152
Issue number8
DOIs
StatePublished - Dec 1 2007
Externally publishedYes

Fingerprint

TIE-2 Receptor
Sulindac
Angiopoietin-1
Human Umbilical Vein Endothelial Cells
Vascular Endothelial Growth Factor A
Blood Vessels
Phosphotransferases
Endothelial Cells
Angiopoietins
Chorioallantoic Membrane
Fibroblast Growth Factor 2
Mitogen-Activated Protein Kinases
Acetic Acid
Cell Movement
Chickens
Intercellular Signaling Peptides and Proteins
Phosphorylation
Ligands
Serum

Keywords

  • Angiogenesis
  • Angiopoietin
  • MAPK
  • Migration
  • Sulindac
  • Tie2

ASJC Scopus subject areas

  • Pharmacology

Cite this

Pyriochou, A., Tsigkos, S., Vassilakopoulos, T., Cottin, T., Zhou, Z., Gourzoulidou, E., ... Papapetropoulos, A. (2007). Anti-angiogenic properties of a sulindac analogue. British Journal of Pharmacology, 152(8), 1207-1214. https://doi.org/10.1038/sj.bjp.0707534

Anti-angiogenic properties of a sulindac analogue. / Pyriochou, A.; Tsigkos, S.; Vassilakopoulos, T.; Cottin, T.; Zhou, Z.; Gourzoulidou, E.; Roussos, C.; Waldmann, H.; Giannis, A.; Papapetropoulos, Andreas.

In: British Journal of Pharmacology, Vol. 152, No. 8, 01.12.2007, p. 1207-1214.

Research output: Contribution to journalArticle

Pyriochou, A, Tsigkos, S, Vassilakopoulos, T, Cottin, T, Zhou, Z, Gourzoulidou, E, Roussos, C, Waldmann, H, Giannis, A & Papapetropoulos, A 2007, 'Anti-angiogenic properties of a sulindac analogue', British Journal of Pharmacology, vol. 152, no. 8, pp. 1207-1214. https://doi.org/10.1038/sj.bjp.0707534
Pyriochou A, Tsigkos S, Vassilakopoulos T, Cottin T, Zhou Z, Gourzoulidou E et al. Anti-angiogenic properties of a sulindac analogue. British Journal of Pharmacology. 2007 Dec 1;152(8):1207-1214. https://doi.org/10.1038/sj.bjp.0707534
Pyriochou, A. ; Tsigkos, S. ; Vassilakopoulos, T. ; Cottin, T. ; Zhou, Z. ; Gourzoulidou, E. ; Roussos, C. ; Waldmann, H. ; Giannis, A. ; Papapetropoulos, Andreas. / Anti-angiogenic properties of a sulindac analogue. In: British Journal of Pharmacology. 2007 ; Vol. 152, No. 8. pp. 1207-1214.
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AU - Vassilakopoulos, T.

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AU - Zhou, Z.

AU - Gourzoulidou, E.

AU - Roussos, C.

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AU - Giannis, A.

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