ArticleCancer research2008
Transient nutlin-3a treatment promotes endoreduplication and the generation of therapy-resistant tetraploid cells.
Article in Cancer research, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 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.
The trial behind it
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
43 citing papers in PubMed, 63 citations in OpenAlex.
- Integrated Genomic and Transcriptomic Profiling of Isolated Trisomies in AML Reveals Cell Cycle Dysregulation and Therapeutic Vulnerabilities.Journal of cellular and molecular medicine · 2025Article
- What Is Apoptosis and Why Is It Inhibited by the Most Important Tumor Suppressor (p53)?International journal of molecular sciences · 2025Review
- Targeting Cardiomyocyte PCNA and POLD1 Prevents Pathologic Myocardial Hypertrophy.Circulation research · 2025Article
- Determinants of Aurora kinase B inhibitor sensitivity in small cell lung cancer.Translational lung cancer research · 2024Article
- p52-ZER6: a determinant of tumor cell sensitivity to MDM2-p53 binding inhibitors.Acta pharmacologica Sinica · 2023Article
- What Are the Reasons for Continuing Failures in Cancer Therapy? Are Misleading/Inappropriate Preclinical Assays to Be Blamed? Might Some Modern Therapies Cause More Harm than Benefit?International journal of molecular sciences · 2022Review
- Resistance mechanisms to inhibitors of p53-MDM2 interactions in cancer therapy: can we overcome them?Cellular & molecular biology letters · 2021Review
- Persistent DNA damage signaling and DNA polymerase theta promote broken chromosome segregation.The Journal of cell biology · 2021Article
- The pseudo-caspase FLIP(L) regulates cell fate following p53 activation.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Dual role of FGF in proliferation and endoreplication of Drosophila tracheal adult progenitor cells.Journal of molecular cell biology · 2020Article
- The long noncoding RNARNA (New York, N.Y.) · 2019Article
- A Cyclin A-Myb-MuvB-Aurora B network regulates the choice between mitotic cycles and polyploid endoreplication cycles.PLoS genetics · 2019Article
- Blocking Mitotic Exit of Ovarian Cancer Cells by Pharmaceutical Inhibition of the Anaphase-Promoting Complex Reduces Chromosomal Instability.Neoplasia (New York, N.Y.) · 2019Article
- DZNep represses Bcl-2 expression and modulates apoptosis sensitivity in response to Nutlin-3a.Cancer biology & therapy · 2018Article
- Endoreplication: The Good, the Bad, and the Ugly.Trends in cell biology · 2018Review
- A DHODH inhibitor increases p53 synthesis and enhances tumor cell killing by p53 degradation blockage.Nature communications · 2018Article
- Losmapimod Overcomes Gefitinib Resistance in Non-small Cell Lung Cancer by Preventing Tetraploidization.EBioMedicine · 2018Article
- Doxorubicin-provoked increase of mitotic activity and concomitant drain of G0-pool in therapy-resistant BE(2)-C neuroblastoma.PloS one · 2018Article
- The IGF-1R/AKT pathway has opposing effects on Nutlin-3a-induced apoptosis.Cancer biology & therapy · 2017Article
- Combination treatment with rucaparib (Rubraca) and MDM2 inhibitors, Nutlin-3 and RG7388, has synergistic and dose reduction potential in ovarian cancer.Oncotarget · 2017Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
p53 Activity is controlled in large part by MDM2, an E3 ubiquitin ligase that binds p53 and promotes its degradation. The MDM2 antagonist Nutlin-3a stabilizes p53 by blocking its interaction with MDM2. Several studies have supported the potential use of Nutlin-3a in cancer therapy. Two different p53 wild-type cancer cell lines (U2OS and HCT116) treated with Nutlin-3a for 24 hours accumulated 2N and 4N DNA content, suggestive of G(1) and G(2) phase cell cycle arrest. This coincided with increased p53 and p21 expression, hypophosphorylation of pRb, and depletion of Cyclin B1, Cyclin A, and CDC2. Upon removal of Nutlin-3a, 4N cells entered S phase and re-replicated their DNA without an intervening mitotic division, a process known as endoreduplication. p53-p21 pathway activation was required for the depletion of Cyclin B1, Cyclin A, and CDC2 in Nutlin-3a-treated cells and for endoreduplication after Nutlin-3a removal. Stable tetraploid clones could be isolated from Nutlin-3a treated cells, and these tetraploid clones were more resistant to ionizing radiation and cisplatin-induced apoptosis than diploid counterparts. These data indicate that transient Nutlin-3a treatment of p53 wild-type cancer cells can promote endoreduplication and the generation of therapy-resistant tetraploid cells. These findings have important implications regarding the use of Nutlin-3a in cancer therapy
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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 OpenQuestion graph.