Pharmacological inhibition of poly(ADP-ribose) polymerase inhibits angiogenesis

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

doi:10.1016/j.bbrc.2006.09.049

Cited by 63 publications

(49 citation statements)

References 28 publications

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“…In addition to its effects on growth, PJ-34 blocked matrix-driven tube-like structure formation. Our findings confirm and extend recent observations that PARP inhibition reduces growth factor-stimulated sprouting from aortic explants and network formation on Matrigel (12,13). Moreover, to determine the effect of PJ-34 on cell motility, we pre-treated cells with the inhibitor and monitored their migration in response to VEGF.…”

Section: Discussionsupporting

confidence: 89%

“…ting that PARP inhibitors block VEGF-and fibroblast growth factor-induced BrdU incorporation in EC (12,13). It should be noted that PJ-34 was found to exert its anti-proliferative effect at lower concentrations than those already reported.…”

Section: Discussionmentioning

confidence: 71%

“…In contrast, the pharmacological inhibition of PARP was shown to inhibit angiogenic sprout formation and the growth factor-stimulated migration and proliferation of EC (12,13). To determine whether inhibition of PARP modifies angiogenesis in vivo, we used a well-established angiogenesis assay, the chicken chorioallantoic membrane assay.…”

Section: Introductionmentioning

confidence: 99%

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Inhibition of angiogenesis by the poly(ADP-ribose) polymerase inhibitor PJ-34

Pyriochou

Oláh²,

Deitch

et al. 2008

Int J Mol Med

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Abstract. Angiogenesis-related treatments have a broad spectrum of potential applications ranging from cancer to macular degeneration, to wound healing. Thus, the identification of pharmacological agents that modulate new blood vessel formation has attracted much attention. In the present study, we investigated the effects of the poly(ADP-ribose) polymerase (PARP) inhibitor PJ-34 [N-(6-Oxo-5,6-dihydro-phenanthridin-2-yl)-N,N-dimethylacetamide] on angiogenesis. Treatment of chicken chorioallantoic membranes (CAM) with PJ-34 reduced vascular length in these tissues; paradoxically, lower doses of PJ-34 (0.03 or 0.3 nmol/cm 2 ) were more effective in inhibiting neovascularisation than higher doses (3 or 30 nmol/cm 2 ). In vitro, incubation of endothelial cells (EC) with PJ-34 (300 nM to 10 μM) inhibited their proliferation in a concentration-dependent manner with maximal inhibition of 22.3% being observed at 10 μM. Capillary morphogenesis of EC grown on Matrigel was also negatively affected by PJ-34. In addition, PJ-34 abolished the migratory response to the prototype angiogenic factor vascular endothelial growth factor (VEGF) and reduced VEGFstimulated activation of members of the mitogen activated protein kinase family (ERK1/2, p38), as well as Akt. PJ-34 also inhibited VEGF-induced NO release and cGMP accumulation. In conclusion, we provide evidence that PARP inhibition blocks angiogenesis-related EC properties by interfering with multiple signalling pathways leading to the inhibition of new blood vessel formation.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 71%

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Inhibition of angiogenesis by the poly(ADP-ribose) polymerase inhibitor PJ-34

Pyriochou

Oláh²,

Deitch

et al. 2008

Int J Mol Med

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“…In certain types of tumors including lung cancer, colon carcinoma and cervical cancer, pArp-1 inhibition was shown to be an effective means of enhancing tumor sensitivity to radiation and chemotherapy (16)(17)(18)(19), also pArp inhibitor could be used as single agents to selectively kill cancers defective in DnA repair, specifically cancers with mutations in the breast cancerassociated genes (BrcA1 and BrcA2) (20,21). Additionally, a number of reports have shown a relationship between pArp and angiogenesis, at least five pArp inhibitors have been efficiently used in vitro (22)(23)(24) to inhibit vascular endothelial growth factor (VegF)-induced proliferation, migration, and tube formation in human umbilical vein endothelial cells (HUVecs). However, whether or not pArp-1 inhibitor is able to suppress tumor cell growth and migration and whether it improves chemotherapeutic effects in human osteosarcoma have rarely been studied.…”

Section: Introductionmentioning

confidence: 99%

The poly(ADP-ribose) polymerase-1 inhibitor 3-aminobenzamide suppresses cell growth and migration, enhancing suppressive effects of cisplatin in osteosarcoma cells

Zheng

Xu²,

Peng³

et al. 2011

Oncol Rep

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Abstract. pharmacological inhibition of DnA repair pathways has been emerging as an effective tool for cancer treatment. poly(ADp-ribose) polymerase (pArp) is involved in DnA repair and transcriptional regulation and is now recognized as a key regulator of cell survival and cell death. In vitro and in vivo data suggest that pArp inhibitors could be used not only as chemo/radiotherapy sensitizers but also as single agents to selectively kill cancer cells in certain types of tumors. In the present study, we investigate the effects of 3-aminobenzamide (3-AB), a potent inhibitor of pArp, on human osteosarcoma cells and whether or not it can sensitize the tumor cells to chemotherapeutic agents. the results indicated that 3-AB suppressed U2os cell growth in a time-and dose-dependent manner, and the suppressive effects of 3-AB were associated with increased cell apoptosis. In addition, 3-AB suppressed cell invasion in vitro and enhanced the suppressive effects of cisplatin in U2os cells. our work suggests that this pArp-1 inhibitor may be developed into an effective agent for the treatment of human osteosarcoma.

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“…In addition, it has been shown that that PARP inhibitors can inhibit the formation of blood vessels. Rajesh et al 16 reported that PARP inhibitors PJ34 and 3-aminobenzamide inhibited migration of vascular endothelial growth factor (VEGF)-induced human umbilical vein endothelial cells (HUVECs), and Pyriochou et al 17 demonstrated that PJ34 could inhibit HUVEC migration induced by VEGF, the nitric oxide donor DETA-NO or BAY41-2272. Therefore, it is possible that PARP-1 inhibitors may have inhibitory effects on ovarian cancer cell proliferation and invasion.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of proliferation and invasiveness of ovarian cancer C13* cells by a poly(ADP-ribose) polymerase inhibitor and the role of nuclear factor-κB

Wang

et al. 2013

J Int Med Res

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Objective: To investigate the effect of the poly(ADP-ribose) polymerase-1 (PARP-1) inhibitor PJ34 on the proliferation and invasiveness of ovarian cancer C13* cells and the role of nuclear factor-kB (NF-kB). Methods: Proliferation of C13* cells was measured using a 3 -(4,5-dimethylthazol-2-yl)-2,5-diphenyl tetrazolium bromide assay after incubation with PJ34 at different concentrations and for different treatment durations. In addition, expression of PARP-1 and the NF-kB p65 subunit after treatment with PJ34 was measured using Western blot and immunocytochemistry. The effect of PJ34 on cell invasiveness was examined using a transwell invasion assay. Results: PJ34 inhibited proliferation of C13* cells in a time-and dose-dependent manner. PJ34 treatment was also associated with a dose-dependent decrease in PARP-1 and NF-kB p65 expression and attenuated invasiveness of C13* cells. PARP-1 expression was positively correlated with NF-kB p65 expression. Conclusion: The PARP-1 inhibitor PJ34 can markedly inhibit the proliferation and invasiveness of C13* cells, possibly due to PARP-1-mediated attenuation of NF-kB activity.

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Pharmacological inhibition of poly(ADP-ribose) polymerase inhibits angiogenesis

Cited by 63 publications

References 28 publications

Inhibition of angiogenesis by the poly(ADP-ribose) polymerase inhibitor PJ-34

Inhibition of angiogenesis by the poly(ADP-ribose) polymerase inhibitor PJ-34

The poly(ADP-ribose) polymerase-1 inhibitor 3-aminobenzamide suppresses cell growth and migration, enhancing suppressive effects of cisplatin in osteosarcoma cells

Inhibition of proliferation and invasiveness of ovarian cancer C13* cells by a poly(ADP-ribose) polymerase inhibitor and the role of nuclear factor-κB

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