ArticleJournal of cancer research and clinical oncology2020
Anticancer effects of the PLK4 inhibitors CFI-400945 and centrinone in Ewing's sarcoma cells.
Article in Journal of cancer research and clinical oncology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 20 citations in OpenAlex.
- TH-302 (evofosfamide) monotherapy exerts anticancer activity in Ewing's sarcoma cells under hypoxia.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Article
- Polo-like kinase 4 (PLK4) as a therapeutic target in breast cancer.Carcinogenesis · 2025Review
- Role of PLK4 inhibition in cancer therapy.Cancer metastasis reviews · 2025Review
- Polyploidy in Cancer: Causal Mechanisms, Cancer-Specific Consequences, and Emerging Treatments.Molecular cancer therapeutics · 2024Review
- Synergistic anticancer activity of combined ATR and ribonucleotide reductase inhibition in Ewing's sarcoma cells.Journal of cancer research and clinical oncology · 2023Article
- Downregulation of PLK4 expression induces apoptosis and G0/G1-phase cell cycle arrest in keloid fibroblasts.Cell proliferation · 2022Article
- Novel Targeted Therapeutic Strategies for Ewing Sarcoma.Cancers · 2022Review
- Repair of Spinal Cord Injury by Inhibition of PLK4 Expression Through Local Delivery of siRNA-Loaded Nanoparticles.Journal of molecular neuroscience : MN · 2022Article
- Effects of the PLK4 inhibitor Centrinone on the biological behaviors of acute myeloid leukemia cell lines.Frontiers in genetics · 2022Article
- Down-regulation of Polo-like kinase 4 (PLK4) induces G1 arrest via activation of the p38/p53/p21 signaling pathway in bladder cancer.FEBS open bio · 2021Article
- Inhibition of Polo-like kinase 4 induces mitotic defects and DNA damage in diffuse large B-cell lymphoma.Cell death & disease · 2021Article
- Role of Polo-Like Kinase 4 (PLK4) in Epithelial Cancers and Recent Progress in its Small Molecule Targeting for Cancer Management.Molecular cancer therapeutics · 2021Review
- Cooperative treatment effectiveness of ATR and HSP90 inhibition in Ewing's sarcoma cells.Cell & bioscience · 2021Article
- PLK4 is a potential therapeutic target in nonmelanoma skin cancers: Evidence from molecular and in vivo studies.Photochemistry and photobiologyArticle
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposePolo-like kinase 4 (PLK4) inhibitors, such as CFI-400945 and centrinone, are emerging as promising antineoplastic agents. However, their effectiveness against Ewing's sarcoma, a highly aggressive childhood cancer, remains to be established.
methodsCFI-400945 and centrinone were tested in three Ewing's sarcoma cell lines with different TP53 status. Effects were assessed by flow-cytometric analyses of cell death, dissipation of the mitochondrial transmembrane potential and cell cycle distribution, by cell viability assay as well as by caspase 3/7 activity measurement, by immunoblotting and by immunofluorescence microscopy.
resultsCFI-400945 and centrinone elicited cell death in p53 wild-type and mutant Ewing's sarcoma cells. Both agents induced mitochondrial membrane depolarisation, caspase 3/7 activation, PARP1 cleavage and DNA fragmentation, indicating an apoptotic form of cell death. In addition, the PLK4 inhibitors induced a G2/M cell cycle arrest, particularly when cell killing was attenuated by the pan-caspase inhibitor z-VAD-fmk. Moreover, CFI-400945 treatment produced polyploidy.
conclusionOur findings show that PLK4 inhibitors were effective against Ewing's sarcoma cells in vitro and thus provide a rationale for their evaluation in vivo.
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