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

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 devel- oped 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 in- hibitor 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 to- gether, 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.