1. Poly(ADP-ribose) polymerase (PARP) inhibition or PARP-1 gene deletion reduces angiogenesis
- Author
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Annalisa Susanna Dorio, Jie Zhang, Pedro Miguel Lacal, Antonella Stoppacciaro, Weizheng Xu, Carlo Leonetti, Zhao-Qi Wang, Federica Ruffini, Grazia Graziani, Marco Scarsella, Alessia Muzi, Wokee Min, Lucio Tentori, and Cristina Colarossi
- Subjects
p53 ,Vascular Endothelial Growth Factor A ,Cancer Research ,Poly Adenosine Diphosphate Ribose ,Angiogenesis ,Poly ADP ribose polymerase ,Poly (ADP-Ribose) Polymerase-1 ,Apoptosis ,Angiogenesis Inhibitors ,Cell cycle ,Biology ,Poly(ADP-ribose) Polymerase Inhibitors ,Poly (ADP-Ribose) Polymerase Inhibitor ,Mismatch repair ,Neovascularization ,Bleomycin ,chemistry.chemical_compound ,Mice ,angiogenesis ,anti-angiogenic compounds ,endothelial cells ,parp inhibitors ,poly(adp-ribose) polymerase ,Neoplasms ,medicine ,Animals ,Organic Chemicals ,Cells, Cultured ,Cell Proliferation ,Chromosomal damage ,Tube formation ,Mice, Knockout ,Dose-Response Relationship, Drug ,Neovascularization, Pathologic ,Settore BIO/14 ,Endothelial Cells ,Tubulin Modulators ,Vascular endothelial growth factor ,Endothelial stem cell ,Mice, Inbred C57BL ,Oncology ,chemistry ,PARP inhibitor ,Cell Migration Inhibition ,Cancer research ,medicine.symptom ,Poly(ADP-ribose) Polymerases ,Gene Deletion - 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.
- Published
- 2007