Inhibitors of Poly(ADP-ribose) polymerases (PARPs) have been proposed as promising chemotherapeutic agents in inflammatory, degenerative, and neoplastic diseases. To further substantiate this proposal, we tested the biomolecular effects of PARP-1 inhibitors DPQ and PJ34 on human glioblastoma (GBM) cells, induced to a proinflammatory state with Lipopolysaccharide (LPS) and Interferon-γ (INF-γ). PARP-1 expression was evaluated by laser scanning confocal microscopy (LSM); nitrite production, LDH release, cell viability were also determined. LSM of A172, SNB-19, CAS-1 cells demonstrated that DPQ and PJ34 downregulate PARP-1 expression; they also cause a decrease of LDH release and nitrite production, while increasing cell viability. Similar effects were caused in all three cell lines also by N-mono-methyl-arginine (NMMA), a well known iNOS inhibitor, and by L-carnosine and trehalose, two antioxidant molecules. These results demonstrate that, similar to other well characterised drugs, DPQ and PJ34 reduce cell inflammation and damage ensuing PARP-1 overexpression, while they increase cell survival: this suggests their potential exploitation in clinical Medicine.
|Titolo:||PARP-1 Inhibitors DPQ and PJ-34 Negatively Modulate Proinflammatory Commitment of Human Glioblastoma Cells.|
|Data di pubblicazione:||2013|
|Appare nelle tipologie:||1.1 Articolo in rivista|