ArticleFrontiers in oncology2021
Inhibition of Poly ADP-Ribose Glycohydrolase Sensitizes Ovarian Cancer Cells to Poly ADP-Ribose Polymerase Inhibitors and Platinum Agents.
Article in Frontiers in oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 11 citations in OpenAlex.
- FET proteins and PARylation-dependent condensates promote replication fork reversal and genome stability.Nature communications · 2026Article
- Future of PARP inhibitors in cancer treatment: overcoming resistance and enhancing efficacy with combination therapies.Journal of Zhejiang University. Science. B · 2025Review
- Loss-of-function genetic screen unveils synergistic efficacy of PARG inhibition with combined 5-fluorouracil and irinotecan treatment in colorectal cancer.Clinical and translational medicine · 2025Article
- Prospects for PARG inhibitors in cancer therapy.Journal of molecular cell biology · 2025Review
- ADP-ribose hydrolases: biological functions and potential therapeutic targets.Expert reviews in molecular medicine · 2024Review
- CHK1 inhibitor induced PARylation by targeting PARG causes excessive replication and metabolic stress and overcomes chemoresistance in ovarian cancer.Cell death discovery · 2024Article
- Synergistic Effect of Ubiquitin-Specific Protease 14 and Poly(ADP-Ribose) Glycohydrolase Co-Inhibition in BRCA1-Mutant, Poly(ADP-Ribose) Polymerase Inhibitor-Resistant Triple-Negative Breast Cancer Cells.OncoTargets and therapy · 2024Article
- Inhibition of nicotinamide dinucleotide salvage pathway counters acquired and intrinsic poly(ADP-ribose) polymerase inhibitor resistance in high-grade serous ovarian cancer.Scientific reports · 2023Article
- Update on poly(ADP-ribose) polymerase inhibitors resistance in ovarian cancer.Frontiers in pharmacology · 2023Review
- Article
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPoly ADP-ribose glycohydrolase (PARG) is responsible for the catabolism of PARP-synthesized PAR to free ADP-ribose. Inhibition of PARG leads to DNA repair interruption and consequently induces cell death. This study aims to evaluate the effect of a PARG inhibitor (PARGi) on epithelial ovarian cancer (OC) cell lines, alone and in combination with a PARP inhibitor (PARPi) and/or Cisplatin.
methodsPARG mRNA levels were studied in three different OC datasets: TCGA, Hendrix, and Meyniel. PARG protein levels were assessed in 100 OC specimens from our bio-bank. The therapeutic efficacy of PARGi was assessed using cell migration and clonogenic formation assays. Flow cytometry was used to evaluate the cell apoptosis rate and the changes in the cell cycle.
resultsPARG protein was highly expressed in 34% of the OC tumors and low expression was found in another 9%. Similarly, Hendrix, Meyneil and TCGA databases showed a significant up-regulation in PARG mRNA expression in OC samples as compared to normal tissue (P=0.001, P=0.005, P=0.005, respectively). The use of PARGi leads to decreased cell migration. PARGi in combination with PARPi or Cisplatin induced decreased survival of cells as compared to each drug alone. In the presence of PARPi and Cisplatin, PARG knockdown cell lines showed significant G2/M cell cycle arrest and cell death induction.
conclusionsPARG inhibition appears as a complementary strategy to PARP inhibition in the treatment of ovarian cancer, especially in the presence of homologous recombination defects.
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