Glioblastomas are widely characterised by the mutation of the p53 gene and p53 disruption sensitizes glioblastoma cells to DNA topoisomerase I (TOPO I) inhibitor-mediated apoptosis. We investigated the effects of combined treatments with the DNA topoisomerase I inhibitor Topotecan and the poly(ADPR)polymerase-1 inhibitor NU1025 in D54p53wt and U251p53mut glioblastoma cell lines. Analysis of cell growth and cell cycle kinetics showed a synergistic anti-proliferative effect of 10 nM TPT and 10 μM NU1025 and a G2/M block of the cell cycle. We also evaluated, the influence of TPT+/−NU1025 treatment on PARP-1 and p53 activity. We got evidences of a TPT-dependent increase of PARP-1 auto-modification level in both the cells. Moreover, in the D54p53wt cells we found that in co-treatments NU1025 incremented the TPT-dependent stimulation of p53 transcriptional activity and increased the p21 nuclear amount. Conversely, in U251p53mut cells we found that NU1025 incremented the TPT-dependent apoptosis characterised by PARP-1 proteolysis. Our findings suggest that the modulation of PARP-1 can be considered a strategy in the potentiation of the chemotherapeutic action of TOPO I poisons in glioblastoma cells apart from their p53 status.

Poly(ADPR)polymerase-1 signalling of the DNA damage induced by DNA topoisomerase I poison in D54p53wt and U251p53mut glioblastoma cell lines / Cimmino, Gabriella; Pepe, Stefano; Laus, Gianluca; M., Chianese; D., Prece; R., Penitente; Quesada, PIERINA MARIA. - In: PHARMACOLOGICAL RESEARCH. - ISSN 1043-6618. - STAMPA. - 55:1(2007), pp. 49-56. [10.1016/j.phrs 2006.10.005]

Poly(ADPR)polymerase-1 signalling of the DNA damage induced by DNA topoisomerase I poison in D54p53wt and U251p53mut glioblastoma cell lines.

CIMMINO, GABRIELLA;PEPE, STEFANO;LAUS, GIANLUCA;QUESADA, PIERINA MARIA
2007

Abstract

Glioblastomas are widely characterised by the mutation of the p53 gene and p53 disruption sensitizes glioblastoma cells to DNA topoisomerase I (TOPO I) inhibitor-mediated apoptosis. We investigated the effects of combined treatments with the DNA topoisomerase I inhibitor Topotecan and the poly(ADPR)polymerase-1 inhibitor NU1025 in D54p53wt and U251p53mut glioblastoma cell lines. Analysis of cell growth and cell cycle kinetics showed a synergistic anti-proliferative effect of 10 nM TPT and 10 μM NU1025 and a G2/M block of the cell cycle. We also evaluated, the influence of TPT+/−NU1025 treatment on PARP-1 and p53 activity. We got evidences of a TPT-dependent increase of PARP-1 auto-modification level in both the cells. Moreover, in the D54p53wt cells we found that in co-treatments NU1025 incremented the TPT-dependent stimulation of p53 transcriptional activity and increased the p21 nuclear amount. Conversely, in U251p53mut cells we found that NU1025 incremented the TPT-dependent apoptosis characterised by PARP-1 proteolysis. Our findings suggest that the modulation of PARP-1 can be considered a strategy in the potentiation of the chemotherapeutic action of TOPO I poisons in glioblastoma cells apart from their p53 status.
2007
Poly(ADPR)polymerase-1 signalling of the DNA damage induced by DNA topoisomerase I poison in D54p53wt and U251p53mut glioblastoma cell lines / Cimmino, Gabriella; Pepe, Stefano; Laus, Gianluca; M., Chianese; D., Prece; R., Penitente; Quesada, PIERINA MARIA. - In: PHARMACOLOGICAL RESEARCH. - ISSN 1043-6618. - STAMPA. - 55:1(2007), pp. 49-56. [10.1016/j.phrs 2006.10.005]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/108888
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