ArticleCancer science2009
Cyclin-dependent kinase 1 inhibitor RO-3306 enhances p53-mediated Bax activation and mitochondrial apoptosis in AML.
Article in Cancer science, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 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
28 citing papers in PubMed, 49 citations in OpenAlex.
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- Adrenocortical carcinoma survival gene HMMR was identified as being targeted by fluorouracil and epirubicin using a gene coexpression network-based drug repositioning strategy.Scientific reports · 2025Article
- TOR1 AIP1 interacts with p53 to enhance cell cycle dysregulation in prostate cancer progression.Molecular and cellular biochemistry · 2025Article
- Inhibition of CDK1 by RO-3306 Exhibits Anti-Tumorigenic Effects in Ovarian Cancer Cells and a Transgenic Mouse Model of Ovarian Cancer.International journal of molecular sciences · 2023Article
- Nano-Zirconium Dioxide Catalyzed Multicomponent Synthesis of Bioactive Pyranopyrazoles That Target Cyclin Dependent Kinase 1 in Human Breast Cancer Cells.Biomedicines · 2023Article
- SUMOylation patterns and signature characterize the tumor microenvironment and predict prognosis in lung adenocarcinoma.Frontiers in cell and developmental biology · 2023Article
- A compendium of Androgen Receptor Variant 7 target genes and their role in Castration Resistant Prostate Cancer.Frontiers in oncology · 2023Review
- CENPF/CDK1 signaling pathway enhances the progression of adrenocortical carcinoma by regulating the G2/M-phase cell cycle.Journal of translational medicine · 2022Article
- Establishment of a Prognostic Prediction and Drug Selection Model for Patients with Clear Cell Renal Cell Carcinoma by Multiomics Data Analysis.Oxidative medicine and cellular longevity · 2022Article
- Synthetic Heterocyclic Derivatives as Kinase Inhibitors Tested for the Treatment of Neuroblastoma.Molecules (Basel, Switzerland) · 2021Review
- EMS1/DLL4-Notch Signaling Axis Augments Cell Cycle-Mediated Tumorigenesis and Progress in Human Adrenocortical Carcinoma.Frontiers in oncology · 2021Article
- DNA damage response signaling pathways and targets for radiotherapy sensitization in cancer.Signal transduction and targeted therapy · 2020Review
- Wnt/β-Catenin in Acute Kidney Injury and Progression to Chronic Kidney Disease.Seminars in nephrology · 2020Review
- The balance between mitotic death and mitotic slippage in acute leukemia: a new therapeutic window?Journal of hematology & oncology · 2019Review
- Cross-talk between Myc and p53 in B-cell lymphomas.Chronic diseases and translational medicine · 2019Article
- Combined venetoclax and alvocidib in acute myeloid leukemia.Oncotarget · 2017Article
- Renoprotective effect of erythropoietin in zebrafish after administration of gentamicin: an immunohistochemical study for β-catenin and c-kit expression.Journal of nephrology · 2017Article
- Mechanisms responsible for the synergistic antileukemic interactions between ATR inhibition and cytarabine in acute myeloid leukemia cells.Scientific reports · 2017Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Cyclin-dependent kinase (CDK) 1 and the murine double minute 2 homolog (MDM2)-p53 interaction are potential therapeutic targets in cancer, and their inhibition has been reported to be more proapoptotic in malignant cells compared to normal cells. We investigated the effect of CDK1 inhibition on p53 signaling after simultaneous dual blockade using the CDK1 inhibitor RO-3306 and the MDM2 inhibitor Nutlin-3 in AML. Treatment of growing AML cells with RO-3306 induced G2/M-phase cell cycle arrest and apoptosis in a dose- and time-dependent manner. We found that RO-3306 acts cooperatively with Nutlin-3 to induce mitochondrial apoptosis in a cell cycle-independent fashion. RO-3306 downregulated expression of the antiapoptotic proteins Bcl-2 and survivin and blocked p53-mediated induction of p21 and MDM2. CDK1 siRNA experiments showed that reduced CDK1 expression affects p53-induced p21 transactivation. We suggest that RO-3306 actively enhances downstream p53 signaling to promote apoptosis and that a combination strategy aimed at both inhibiting CDK1 and activating p53 signaling is potentially effective in AML, where TP53 mutations are rare and downstream p53 signaling is intact.
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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.