TY - JOUR
T1 - Poly(ADP-ribose)polymerase inhibition decreases angiogenesis
AU - Rajesh, Mohanraj
AU - Mukhopadhyay, Partha
AU - Godlewski, Grzegorz
AU - Bátkai, Sándor
AU - Haskó, György
AU - Liaudet, Lucas
AU - Pacher, Pál
N1 - Funding Information:
This study was supported by the Intramural Research Program of NIH/NIAAA (to P.P.). Dr. Pacher wants to dedicate this work to his beloved mother Iren.
PY - 2006/12/1
Y1 - 2006/12/1
N2 - 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. We have recently demonstrated that PARP inhibition with 3-aminobenzamide or PJ-34 reduced vascular endothelial growth factor (VEGF)-induced proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs) in vitro. Here, we show dose-dependent reduction of VEGF- and basic fibroblast growth factor (bFGF)-induced proliferation, migration, and tube formation of HUVECs in vitro by two potent PARP inhibitors 5-aminoisoquinolinone-hydrochloride (5-AIQ) and 1,5-isoquinolinediol (IQD). Moreover, PARP inhibitors prevented 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.
AB - 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. We have recently demonstrated that PARP inhibition with 3-aminobenzamide or PJ-34 reduced vascular endothelial growth factor (VEGF)-induced proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs) in vitro. Here, we show dose-dependent reduction of VEGF- and basic fibroblast growth factor (bFGF)-induced proliferation, migration, and tube formation of HUVECs in vitro by two potent PARP inhibitors 5-aminoisoquinolinone-hydrochloride (5-AIQ) and 1,5-isoquinolinediol (IQD). Moreover, PARP inhibitors prevented 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.
KW - 1,5-Isoquinolinediol (IQD)
KW - 5-Aminoisoquinolinone-hydrochloride (5-AIQ)
KW - Angiogenesis
KW - Aortic ring assay
KW - Cancer
KW - HUVEC
KW - Migration
KW - Poly(ADP-ribose)polymerase (PARP)
KW - Proliferation
KW - Tube formation
UR - http://www.scopus.com/inward/record.url?scp=33750046338&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33750046338&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2006.09.160
DO - 10.1016/j.bbrc.2006.09.160
M3 - Article
C2 - 17046715
AN - SCOPUS:33750046338
SN - 0006-291X
VL - 350
SP - 1056
EP - 1062
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 4
ER -