In PARP inhibitor-resistant A172 glioblastoma cells, our PARG inhibitor shows comparable killing to Nedaplatin, providing further proof-of-concept that selectively inhibiting PARG can impair cancer cell survival.
Furthermore, our results revealed the ability of luteolin to induce caspase and PARP cleavages in glioblastoma cells in addition to promoting cell cycle arrest.
A potential clinical scenario, intratumoral convection-enhanced delivery, was mimicked using an orthotopic glioblastoma model combined with an implanted osmotic pump system to study local administration of <sup>131</sup>I-PARPi (PARPi is PARP inhibitor).
Moreover, NK-EM cytotoxicity for glioblastoma cells that related with decreased levels of the cell survival markers p-ERK and p-AKT, and increased levels of apoptosis protein markers cleaved-caspase 3, cytochrome-c and cleaved-PARP was confirmed.
ABT-888 is a PARP inhibitor undergoing extensive clinical evaluation in glioblastoma, because it may synergize with the standard-of-care temozolomide (TMZ).