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Poly(ADP‐ribose)polymerase inhibition decreases angiogenesis.
Author(s) -
Rajesh Mohanraj,
Mukhopadhyay Partha,
Godlewski Grzegorz,
Bátkai Sandor,
Pacher Pal
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1136.8
Subject(s) - poly adp ribose polymerase , angiogenesis , ex vivo , in vivo , cancer research , pharmacology , vascular endothelial growth factor , basic fibroblast growth factor , in vitro , neovascularization , polymerase , chemistry , biology , enzyme , growth factor , biochemistry , vegf receptors , receptor , microbiology and biotechnology
Inhibitors of poly(ADP‐ribose)polymerase (PARP), a nuclear enzyme involved in regulating cell death and cellular responses to DNA repair, show considerable promise in the treatment of cancer both in monotherapy as well as in combination with chemotherapeutic agents and radiation. Here, we show dose‐dependent reduction of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF)‐induced proliferation, migration, and tube formation of HUVECs in vitro by various PARP inhibitors (3‐aminobenzamide or PJ‐34, 5‐aminoisoquinolinone‐hydrochloride (5‐AIQ) and 1,5‐isoquinolinediol (IQD). Moreover, PARP inhibitors decrease the sprouting of rat aortic ring explants in an ex vivo assay of angiogenesis. These results establish the novel concept that PARP inhibitors have antiangiogenic effects, which may have tremendous clinical implications for the treatment of various cancers, tumor metastases, and certain retinopathies.