title: Poly(ADP-ribosylation) and neoplastic transformation: effect of PARP inhibitors.
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(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.
authors.forename: Francesca
authors.initials: F
authors.lastname: Donà
authors.forename: Ilaria
authors.initials: I
authors.lastname: Chiodi
authors.forename: Cristina
authors.initials: C
authors.lastname: Belgiovine
authors.forename: Tatiana
authors.initials: T
authors.lastname: Raineri
authors.forename: Roberta
authors.initials: R
authors.lastname: Ricotti
authors.forename: Chiara
authors.initials: C
authors.lastname: Mondello
authors.affiliation: Istituto di Genetica Molecolare CNR, Via Abbiategrasso 207, 27100 Pavia, Italy. scovassi@igm.cnr.it.
authors.forename: Anna Ivana
authors.initials: AI
authors.lastname: Scovassi
mesh_terms: D000818:Animals; D001549:Benzamides / Q000494:pharmacology / Q000627:therapeutic use; D002471:Cell Transformation, Neoplastic / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D016615:Telomere / Q000187:drug effects / Q000378:metabolism
chemical_list: D001549:Benzamides; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; C025160:3-aminobenzamide; D011065:Poly(ADP-ribose) Polymerases