TY - JOUR
T1 - Poly(ADP-ribose) polymerase (PARP) inhibition or PARP-1 gene deletion reduces angiogenesis
AU - Tentori, Lucio
AU - Lacal, Pedro Miguel
AU - Muzi, Alessia
AU - Dorio, Annalisa Susanna
AU - Leonetti, Carlo
AU - Scarsella, Marco
AU - Ruffini, Federica
AU - Xu, Weizheng
AU - Min, Wokee
AU - Stoppacciaro, Antonella
AU - Colarossi, Cristina
AU - Wang, Zhao Qi
AU - Zhang, Jie
AU - Graziani, Grazia
PY - 2007/9
Y1 - 2007/9
N2 - 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.
AB - 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.
KW - Angiogenesis
KW - Anti-angiogenic compounds
KW - Endothelial cells
KW - PARP inhibitors
KW - Poly(ADP-ribose) polymerase
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U2 - 10.1016/j.ejca.2007.07.010
DO - 10.1016/j.ejca.2007.07.010
M3 - Article
C2 - 17714938
AN - SCOPUS:34548514842
SN - 0959-8049
VL - 43
SP - 2124
EP - 2133
JO - European Journal of Cancer
JF - European Journal of Cancer
IS - 14
ER -