ArticleOncotarget2015
Inhibition of Bcl-xL overcomes polyploidy resistance and leads to apoptotic cell death in acute myeloid leukemia cells.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 32 citations in OpenAlex.
- Modelling the monstrosities: experimental and computational systems for studying polyploid giant cancer cells.Expert reviews in molecular medicine · 2025Review
- The dual role of whole-genome duplication: biological mechanisms, functional consequences, and detection advances.Acta biochimica et biophysica Sinica · 2025Review
- Zoledronic acid targets chemo-resistant polyploid giant cancer cells.Scientific reports · 2023Article
- Aurora-A/FOXO3A/SKP2 axis promotes tumor progression in clear cell renal cell carcinoma and dual-targeting Aurora-A/SKP2 shows synthetic lethality.Cell death & disease · 2022Article
- Cellular Responses to Platinum-Based Anticancer Drugs and UVC: Role of p53 and Implications for Cancer Therapy.International journal of molecular sciences · 2020Review
- Role of Bcl-2 on drug resistance in breast cancer polyploidy-induced spindle poisons.Oncology letters · 2020Article
- Side-by-side comparison of BH3-mimetics identifies MCL-1 as a key therapeutic target in AML.Cell death & disease · 2019Article
- The balance between mitotic death and mitotic slippage in acute leukemia: a new therapeutic window?Journal of hematology & oncology · 2019Review
- Aurora-A/ERK1/2/mTOR axis promotes tumor progression in triple-negative breast cancer and dual-targeting Aurora-A/mTOR shows synthetic lethality.Cell death & disease · 2019Article
- Role of microRNAs in the resistance of colorectal cancer to chemoradiotherapy.Molecular and clinical oncology · 2018Review
- Antiapoptotic BCL-2 proteins determine sorafenib/regorafenib resistance and BH3-mimetic efficacy in hepatocellular carcinoma.Oncotarget · 2018Article
- Article
- Pyrrolidine dithiocarbamate sensitizes U251 brain glioma cells to temozolomide via downregulation ofOncology letters · 2017Article
- Cell-penetrating peptide conjugates to enhance the antitumor effect of paclitaxel on drug-resistant lung cancer.Drug delivery · 2017Article
- Inhibition of polypyrimidine tract-binding protein 3 induces apoptosis and cell cycle arrest, and enhances the cytotoxicity of 5- fluorouracil in gastric cancer cells.British journal of cancer · 2017Article
- Genomic complexity and dynamics of clonal evolution in childhood acute myeloid leukemia studied with whole-exome sequencing.Oncotarget · 2016Article
- miR-133 regulates Evi1 expression in AML cells as a potential therapeutic target.Scientific reports · 2016Article
- Resistance to Cell Death and Its Modulation in Cancer Stem Cells.Critical reviews in oncogenesis · 2016Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 8 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Small molecular inhibitors or drugs targeting specific molecular alterations are widely used in clinic cancer therapy. Despite the success of targeted therapy, the development of drug resistance remains a challenging problem. Identifying drug resistance mechanisms for targeted therapy is an area of intense investigation, and recent evidence indicates that cellular polyploidy may be involved. Here, we demonstrate that the cell cycle kinase inhibitor, Oxindole-1 (Ox-1), induces mitotic slippage, causing resistant polyploidy in acute myeloid leukemia (AML) cells. Indeed, Ox-1 decreases the kinase activity of CDK1 (CDC2)/cyclin B1, leading to inhibition of Bcl-xL phosphorylation and subsequent resistance to apoptosis. Addition of ABT-263, a Bcl-2 family inhibitor, to Ox-1, or the other polyploidy-inducer, ZM447439 (ZM), produces a synergistic loss of cell viability with greater sustained tumor growth inhibition in AML cell lines and primary AML blasts. Furthermore, genetic knockdown of Bcl-xL, but not Bcl-2, exhibited synergistic inhibition of cell growth in combination with Ox-1 or ZM. These data demonstrate that Bcl-xL is a key factor in polyploidization resistance in AML, and that suppression of Bcl-xL by ABT-263, or siRNAs, may hold therapeutic utility in drug-resistant polyploid AML cells.
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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.