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

被引：13
作者：
Dona, Francesca [1 ]
Chiodi, Ilaria [1 ]
Belgiovine, Cristina [1 ]
Raineri, Tatiana [1 ]
Ricotti, Roberta [1 ]
Mondello, Chiara [1 ]
Scovassi, Anna Ivana [1 ]
机构：
[1] CNR, Ist Genet Mol, I-27100 Pavia, Italy
来源：
CURRENT PHARMACEUTICAL BIOTECHNOLOGY | 2013年 / 14卷 / 05期
关键词：
Neoplastic transformation; PARP inhibitors; Poly(ADP-ribosylation); Telomeres; 3-aminobenzamide; MESSENGER-RNA LEVELS; ADP-RIBOSYL TRANSFERASE; DIPHOSPHATE-RIBOSE) POLYMERASE-1 EXPRESSION; DNA STRAND BREAKS; TELOMERE LENGTH; MALIGNANT MELANOMAS; OXIDATIVE STRESS; CANCER; MODULATION; REPAIR;
D O I：
10.2174/138920101405131111104642
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
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(ADP-ribosylation) 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.
引用
收藏
页码：524 / 536
页数：13
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