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.
PARP-1 Inhibitors DPQ and PJ-34 Negatively Modulate Proinflammatory Commitment of Human Glioblastoma Cells
SCALIA, Marina;SATRIANO, Cristina;RIZZARELLI, Enrico;SPINA, Vittoria Rita Annamaria
2013-01-01
Abstract
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.File | Dimensione | Formato | |
---|---|---|---|
PARP-1 inhibitors DPQ and PJ-34.pdf
solo gestori archivio
Tipologia:
Versione Editoriale (PDF)
Licenza:
NON PUBBLICO - Accesso privato/ristretto
Dimensione
837.71 kB
Formato
Adobe PDF
|
837.71 kB | Adobe PDF | Visualizza/Apri |
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.