Poly(ADP-ribosylation) and Neoplastic Transformation: Effect of PARP Inhibitors

Author(s): Francesca Donà, Ilaria Chiodi, Cristina Belgiovine, Tatiana Raineri, Roberta Ricotti, Chiara Mondello, Anna Ivana Scovassi.

Journal Name: Current Pharmaceutical Biotechnology

Volume 14 , Issue 5 , 2013

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Abstract:

Poly(ADP-ribose) polymerases (PARPs) and poly(ADP-ribosylation) play essential roles in several biological processes, among which neoplastic transformation and telomere maintenance. In this paper, we review the poly(ADPribosylation) process together with the highly appealing use of PARP inhibitors for the treatment of cancer. In addition, we report our results concerning poly(ADP-ribosylation) in a cellular model system for neoplastic transformation developed in our laboratory. Here we show that PARP-1 and PARP-2 expression increases during neoplastic transformation, together with the basal levels of poly(ADP-ribosylation). Furthermore, we demonstrate a greater effect of the PARP inhibitor 3-aminobenzamide (3AB) on cellular viability in neoplastically transformed cells compared to normal fibroblasts and we show that prolonged 3AB administration to tumorigenic cells causes a decrease in telomere length. Taken together, our data support an active involvement of poly(ADP-ribosylation) in neoplastic transformation and telomere length maintenance and confirm the relevant role of poly(ADP-ribosylation) inhibition for the treatment of cancer.

Keywords: Neoplastic transformation, PARP inhibitors, Poly(ADP-ribosylation), Telomeres, 3-aminobenzamide.

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Article Details

VOLUME: 14
ISSUE: 5
Year: 2013
Page: [524 - 536]
Pages: 13
DOI: 10.2174/138920101405131111104642
Price: $58

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