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 microM), 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.

Tentori, L., Lacal, P., Muzi, A., Dorio, A.s., Leonetti, C., Scarsella, M., et al. (2007). Poly(ADP-ribose) polymerase (PARP) inhibition or PARP-1 gene deletion reduces angiogenesis. EUROPEAN JOURNAL OF CANCER, 43(14), 2124-2133 [http://dx.doi.org/10.1016/j.ejca.2007.07.010].

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

TENTORI, LUCIO;MUZI, ALESSIA;DORIO, ANNALISA SUSANNA;GRAZIANI, GRAZIA
2007

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 microM), 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.
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore BIO/14
English
Con Impact Factor ISI
Mismatch repair; p53; Bleomycin; Cell cycle; Apoptosis; Chromosomal damage
Tentori, L., Lacal, P., Muzi, A., Dorio, A.s., Leonetti, C., Scarsella, M., et al. (2007). Poly(ADP-ribose) polymerase (PARP) inhibition or PARP-1 gene deletion reduces angiogenesis. EUROPEAN JOURNAL OF CANCER, 43(14), 2124-2133 [http://dx.doi.org/10.1016/j.ejca.2007.07.010].
Tentori, L; Lacal, P; Muzi, A; Dorio, As; Leonetti, C; Scarsella, M; Ruffini, F; Min, W; Stoppacciaro, A; Colarossi, C; Wang, Z; Zhang, J; Graziani, G
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2108/38009
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