First Author | Tentori L | Year | 2007 |
Journal | Eur J Cancer | Volume | 43 |
Issue | 14 | Pages | 2124-33 |
PubMed ID | 17714938 | Mgi Jnum | J:124866 |
Mgi Id | MGI:3722715 | Doi | 10.1016/j.ejca.2007.07.010 |
Citation | Tentori L, et al. (2007) Poly(ADP-ribose) polymerase (PARP) inhibition or PARP-1 gene deletion reduces angiogenesis. Eur J Cancer 43(14):2124-2133 |
abstractText | 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 (IC(50) on endothelial PARP: 237+/-27nM), at concentrations devoid of cytotoxic effects (0.5-1muM), 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. |