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Breast Cancer Research
Published in: Breast Cancer Research 6/2009

Open Access 01-12-2009 | Research article

A selective eradication of human nonhereditary breast cancer cells by phenanthridine-derived polyADP-ribose polymerase inhibitors

Authors: Dana Inbar-Rozensal, Asher Castiel, Leonid Visochek, David Castel, Françoise Dantzer, Shai Izraeli, Malka Cohen-Armon

Published in: Breast Cancer Research | Issue 6/2009

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Abstract

Introduction

PARP-1 (polyADP-ribose polymerase-1) is known to be activated in response to DNA damage, and activated PARP-1 promotes DNA repair. However, a recently disclosed alternative mechanism of PARP-1 activation by phosphorylated externally regulated kinase (ERK) implicates PARP-1 in a vast number of signal-transduction networks in the cell. Here, PARP-1 activation was examined for its possible effects on cell proliferation in both normal and malignant cells.

Methods

In vitro (cell cultures) and in vivo (xenotransplants) experiments were performed.

Results

Phenanthridine-derived PARP inhibitors interfered with cell proliferation by causing G2/M arrest in both normal (human epithelial cells MCF10A and mouse embryonic fibroblasts) and human breast cancer cells MCF-7 and MDA231. However, whereas the normal cells were only transiently arrested, G2/M arrest in the malignant breast cancer cells was permanent and was accompanied by a massive cell death. In accordance, treatment with a phenanthridine-derived PARP inhibitor prevented the development of MCF-7 and MDA231 xenotransplants in female nude mice. Quiescent cells (neurons and cardiomyocytes) are not impaired by these PARP inhibitors.

Conclusions

These results outline a new therapeutic approach for a selective eradication of abundant nonhereditary human breast cancers.
Appendix
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Metadata
Title
A selective eradication of human nonhereditary breast cancer cells by phenanthridine-derived polyADP-ribose polymerase inhibitors
Authors
Dana Inbar-Rozensal
Asher Castiel
Leonid Visochek
David Castel
Françoise Dantzer
Shai Izraeli
Malka Cohen-Armon
Publication date
01-12-2009
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 6/2009
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/bcr2445

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