Poly(ADP-ribose) polymerase (PARP) inhibition or PARP-1 gene deletion reduces angiogenesis

Lucio Tentori, Pedro Miguel Lacal, Alessia Muzi, Annalisa Susanna Dorio, Carlo Leonetti, Marco Scarsella, Federica Ruffini, Weizheng Xu, Wokee Min, Antonella Stoppacciaro, Cristina Colarossi, Zhao Qi Wang, Jie Zhang, Grazia Graziani

Research output: Contribution to journalArticle

Abstract

Poly(ADP-ribose) polymerase (PARP)-1 has recently been shown to promote tumour progression. Since angiogenesis is an essential requirement for tumour growth, we examined whether PARP inhibition/deletion might affect endothelial cell functions. To this end, the influence of PARP inhibitors on endothelial cell proliferation, migration, tube formation and angiogenesis in PARP-1 knock-out mice, using an in vivo matrigel plug assay, was investigated. The results indicated that the PARP inhibitor GPI 15427 (IC50 on endothelial PARP: 237 ± 27 nM), at concentrations devoid of cytotoxic effects (0.5-1 μM), abrogated migration in response to vascular endothelial growth factor or placenta growth factor, hampered formation of tubule-like networks and impaired angiogenesis in vivo. The anti-angiogenic effect of the PARP inhibitor was confirmed in PARP-1 knock-out mice that displayed a defect of angiogenesis induced by growth factors. These results provide evidence for targeting PARP for anti-angiogenesis, adding novel therapeutic implications to the use of PARP inhibitors in cancer treatment.

Original languageEnglish (US)
Pages (from-to)2124-2133
Number of pages10
JournalEuropean Journal of Cancer
Volume43
Issue number14
DOIs
StatePublished - Sep 2007
Externally publishedYes

Keywords

  • Angiogenesis
  • Anti-angiogenic compounds
  • Endothelial cells
  • PARP inhibitors
  • Poly(ADP-ribose) polymerase

ASJC Scopus subject areas

  • Cancer Research
  • Hematology
  • Oncology

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  • Cite this

    Tentori, L., Lacal, P. M., Muzi, A., Dorio, A. S., Leonetti, C., Scarsella, M., Ruffini, F., Xu, W., Min, W., Stoppacciaro, A., Colarossi, C., Wang, Z. Q., Zhang, J., & Graziani, G. (2007). Poly(ADP-ribose) polymerase (PARP) inhibition or PARP-1 gene deletion reduces angiogenesis. European Journal of Cancer, 43(14), 2124-2133. https://doi.org/10.1016/j.ejca.2007.07.010