Polθ Inhibitor (ART558) Demonstrates a Synthetic Lethal Effect with PARP and RAD52 Inhibitors in Glioblastoma Cells.

ABSTRACT: DNA repair proteins became the popular targets in research on cancer treatment. In our studies we hypothesized that inhibition of DNA polymerase theta (Polθ) and its combination with Poly (ADP-ribose) polymerase 1 (PARP1) or RAD52 inhibition and the alkylating drug temozolomide (TMZ) has an anticancer effect on glioblastoma cells (GBM21), whereas it has a low impact on normal human astrocytes (NHA). The effect of the compounds was assessed by analysis of cell viability, apoptosis, proliferation, DNA damage and cell cycle distribution, as well as gene expression. The main results show that Polθ inhibition causes a significant decrease in glioblastoma cell viability. It induces apoptosis, which is accompanied by a reduction in cell proliferation and DNA damage. Moreover, the effect was stron

SUBMITTER: Barszczewska-Pietraszek G 

PROVIDER: S-EPMC11395082 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature