ArticlePloS one2019
Additive effects of a small molecular PCNA inhibitor PCNA-I1S and DNA damaging agents on growth inhibition and DNA damage in prostate and lung cancer cells.
Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
15 citing papers in PubMed, 24 citations in OpenAlex.
- Modification of PCNA by ISG15 plays a crucial role in porcine deltacoronavirus infection.Veterinary research · 2026Article
- Targeting Cancer-Associated PCNA with AOH1996 Induces Mitotic Catastrophe and Enhances Cisplatin Therapy in Cervical Cancer.Cancer research communications · 2026Article
- Comparative Transcriptomic Analysis Reveals Divergent Host Cell Responses to Classical and Variant Pseudorabies Virus Strains.Veterinary sciences · 2026Article
- Senescence-related gene signature predicts prostate cancer progression and identifies PCNA as a therapeutic target via multi-omics machine learning integration.British journal of cancer · 2026Article
- Article
- Transforming cancer immunotherapy: integration of distinct immune-based approaches as redefined dual immunotherapy with potential third-sensitizer.Experimental hematology & oncology · 2025Review
- The PCNA inhibitor AOH1996 suppresses cancer stemness and enhances anti-PD1 immunotherapy in squamous cell carcinoma.Stem cell research & therapy · 2025Article
- Targeting PCNA/AR interaction inhibits AR-mediated signaling in castration resistant prostate cancer cells.Oncotarget · 2025Article
- Review
- Proliferating cell nuclear antigen inhibitors block distinct stages of herpes simplex virus infection.PLoS pathogens · 2023Article
- NKp44-Derived Peptide Used in Combination Stimulates Antineoplastic Efficacy of Targeted Therapeutic Drugs.International journal of molecular sciences · 2022Article
- Characterization of the Interaction Between SARS-CoV-2 Membrane Protein (M) and Proliferating Cell Nuclear Antigen (PCNA) as a Potential Therapeutic Target.Frontiers in cellular and infection microbiology · 2022Article
- Review
- Proliferating cell nuclear antigen directly interacts with androgen receptor and enhances androgen receptor‑mediated signaling.International journal of oncology · 2021Article
- Potential therapeutic targets shared between leishmaniasis and cancer.Parasitology · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Proliferating cell nuclear antigen (PCNA) is essential for DNA replication and repair, and cell growth and survival. Previously, we identified a novel class of small molecules that bind directly to PCNA, stabilize PCNA trimer structure, reduce chromatin-associated PCNA, selectively inhibit tumor cell growth, and induce apoptosis. The purpose of this study was to investigate the combinatorial effects of lead compound PCNA-I1S with DNA damaging agents on cell growth, DNA damage, and DNA repair in four lines of human prostate and lung cancer cells. The DNA damage agents used in the study include ionizing radiation source cesium-137 (Cs-137), chemotherapy drug cisplatin (cisPt), ultraviolet-C (UV-C), and oxidative compound H2O2. DNA damage was assessed using immunofluorescent staining of γH2AX and the Comet assay. The homologous recombination repair (HRR) was determined using a plasmid-based HRR reporter assay and the nucleotide excision repair (NER) was indirectly examined by the removal of UV-induced cyclobutane pyrimidine dimers (CPD). We found that PCNA-I1S inhibited cell growth in a dose-dependent manner and significantly enhanced the cell growth inhibition induced by pretreatment with DNA damaging agents Cs-137 irradiation, UV-C, and cisPt. However, the additive growth inhibitory effects were not observed in cells pre-treated with PCNA-I1S, followed by treatment with cisPt. H2O2 enhanced the level of chromatin-bound PCNA in quiescent cells, which was attenuated by PCNA-I1S. DNA damage was induced in cells treated with either PCNA-I1S or cisPt alone and was significantly elevated in cells exposed to the combination of PCNA-I1S and cisPt. Finally, PCNA-I1S attenuated repair of DNA double strand breaks (DSBs) by HRR and the removal of CPD by NER. These data suggest that targeting PCNA with PCNA-I1S may provide a novel approach for enhancing the efficacy of chemotherapy and radiation therapy in treatment of human prostate and lung cancer.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.