Poly(ADP-ribose)polymerase inhibition decreases angiogenesis

Mohanraj Rajesh, Partha Mukhopadhyay, Grzegorz Godlewski, Sándor Bátkai, György Haskó, Lucas Liaudet, Pál Pacher

Research output: Contribution to journalArticlepeer-review

69 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1056-1062
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume350
Issue number4
DOIs
Publication statusPublished - Dec 1 2006
Externally publishedYes

Keywords

  • 1,5-Isoquinolinediol (IQD)
  • 5-Aminoisoquinolinone-hydrochloride (5-AIQ)
  • Angiogenesis
  • Aortic ring assay
  • Cancer
  • HUVEC
  • Migration
  • Poly(ADP-ribose)polymerase (PARP)
  • Proliferation
  • Tube formation

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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