ArticleCell cycle (Georgetown, Tex.)2012
The induction of polyploidy or apoptosis by the Aurora A kinase inhibitor MK8745 is p53-dependent.
Article in Cell cycle (Georgetown, Tex.), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 54 citations in OpenAlex.
- Phase II study of MLN8237 (Alisertib) in advanced/metastatic sarcoma.Annals of oncology : official journal of the European Society for Medical Oncology · 2016Trial
- Article
- Aurora kinases signaling in cancer: from molecular perception to targeted therapies.Molecular cancer · 2025Review
- Half the Chromosome It Used to Be: Identifying Cancer Treatments Targeting Aneuploid Losses.Genes · 2025Article
- Discovery of a Novel Pseudo-Natural Product Aurora Kinase Inhibitor Chemotype through Morphological Profiling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Drug-resilient Cancer Cell Phenotype Is Acquired via Polyploidization Associated with Early Stress Response Coupled to HIF2α Transcriptional Regulation.Cancer research communications · 2024Article
- Aurora B Inhibitors as Cancer Therapeutics.Molecules (Basel, Switzerland) · 2023Review
- Cisplatin-Resistant Ovarian Cancer Cells Reveal a Polyploid Phenotype with Remarkable Activation of Nuclear Processes.Advanced biomedical research · 2023Article
- Selective Inhibitors of Autophagy Reveal New Link between the Cell Cycle and Autophagy and Lead to Discovery of Novel Synergistic Drug Combinations.ACS chemical biology · 2022Article
- Targeting aurora kinase a (AURKA) in cancer: molecular docking and dynamic simulations of potential AURKA inhibitors.Medical oncology (Northwood, London, England) · 2022Article
- CD44+ and CD133+ Non-Small Cell Lung Cancer Cells Exhibit DNA Damage Response Pathways and Dormant Polyploid Giant Cancer Cell Enrichment Relating to Their p53 Status.International journal of molecular sciences · 2022Article
- Article
- Total synthesis of biselide A.Chemical science · 2021Article
- CRISPR/Cas9 screening identifies a kinetochore-microtubule dependent mechanism for Aurora-A inhibitor resistance in breast cancer.Cancer communications (London, England) · 2021Article
- Targeting AURKA in Cancer: molecular mechanisms and opportunities for Cancer therapy.Molecular cancer · 2021Review
- Aurora Kinase A as a Diagnostic and Prognostic Marker of Malignant Mesothelioma.Frontiers in oncology · 2021Article
- High-throughput Chemical Screening Identifies Focal Adhesion Kinase and Aurora Kinase B Inhibition as a Synergistic Treatment Combination in Ewing Sarcoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Article
- The role of aurora A and polo-like kinases in high-risk lymphomas.Blood advances · 2019Review
- Aurora kinase and FGFR3 inhibition results in significant apoptosis in molecular subgroups of multiple myeloma.Oncotarget · 2018Article
- Phase I study of the aurora A kinase inhibitor alisertib with induction chemotherapy in patients with acute myeloid leukemia.Haematologica · 2017Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aurora kinases are mitotic serine/threonine protein kinases and are attractive novel targets for anticancer therapy. Many small-molecule inhibitors of Aurora kinases are currently undergoing clinical trials. Aurora A kinase is essential for successful mitotic transition. MK8745 is a novel and selective small-molecule inhibitor of Aurora A kinase. MK8745 induced apoptotic cell death in a p53-dependent manner when tested in vitro in cell lines of multiple lineages. Cells expressing wild-type p53 showed a short delay in mitosis followed by cytokinesis, resulting in 2N cells along with apoptosis. However, cells lacking or with mutant p53 resulted in a prolonged arrest in mitosis followed by endoreduplication and polyploidy. Cytokinesis was completely inhibited in p53-deficient cells, as observed by the absence of 2N cell population. The induction of apoptosis in p53-proficient cells was associated with activation of caspase 3 and release of cytochrome c but was independent of p21. Exposure of p53 wild-type cells to MK8745 resulted in the induction of p53 phosphorylation (ser15) and an increase in p53 protein expression. p53-dependent apoptosis by MK8745 was further confirmed in HCT 116 p53(-/-) cells transfected with wild-type p53. Transient knockdown of Aurora A by specific siRNA recapitulated these p53- dependent effects, with greater percent induction of apoptosis in p53 wild-type cells. In conclusion, our studies show p53 as a determining factor for induction of apoptosis vs. polyploidy upon inhibition of Aurora A.
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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 OpenQuestion graph.