Trial reportHaematologica2012
The sorafenib plus nutlin-3 combination promotes synergistic cytotoxicity in acute myeloid leukemic cells irrespectively of FLT3 and p53 status.
Trial report in Haematologica, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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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.
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Who cites it
38 citing papers in PubMed, 50 citations in OpenAlex.
- AcTor, a novel mTOR stimulator, potentiates ixazomib for the treatment of acute myeloid leukemia.Molecular cancer · 2026Article
- AcTor, a novel mTOR stimulator, potentiates ixazomib for the treatment of acute myeloid leukemia.Research square · 2026Article
- Pandora's Box of AML: HowBiomedicines · 2025Review
- Decoding the ubiquitin network: molecular mechanisms and therapeutic vulnerabilities for precision radio-sensitization in cancer.Molecular cancer · 2025Review
- OTU deubiquitinases in cancer pathogenesis and precision therapy.American journal of cancer research · 2025Review
- Microfluidic Fabricated Liposomes for Nutlin-3a Ocular Delivery as Potential Candidate for Proliferative Vitreoretinal Diseases Treatment.International journal of nanomedicine · 2024Article
- Advancements in MDM2 inhibition: Clinical and pre-clinical investigations of combination therapeutic regimens.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2023Review
- miR-221/222 induce instability of p53 By downregulating deubiquitinase YOD1 in acute myeloid leukemia.Cell death discovery · 2023Article
- Dual IKZF2 and CK1α degrader targets acute myeloid leukemia cells.Cancer cell · 2023Article
- In Vitro and In Vivo Modeling of Normal and Leukemic Bone Marrow Niches: Cellular Senescence Contribution to Leukemia Induction and Progression.International journal of molecular sciences · 2022Review
- p53 mApoptosis : an international journal on programmed cell death · 2022Article
- Transcription factors in the pathogenesis of pulmonary arterial hypertension-Current knowledge and therapeutic potential.Frontiers in cardiovascular medicine · 2022Review
- The Role of the CREB Protein Family Members and the Related Transcription Factors in Radioresistance Mechanisms.Life (Basel, Switzerland) · 2021Review
- Resistance mechanisms to inhibitors of p53-MDM2 interactions in cancer therapy: can we overcome them?Cellular & molecular biology letters · 2021Review
- Cell Survival and Cell Death at the Intersection of Autophagy and Apoptosis: Implications for Current and Future Cancer Therapeutics.ACS pharmacology & translational science · 2021Review
- Overcoming of Microenvironment Protection on Primary Chronic Lymphocytic Leukemia Cells after Treatment with BTK and MDM2 Pharmacological Inhibitors.Current oncology (Toronto, Ont.) · 2021Article
- Triangular Relationship between p53, Autophagy, and Chemotherapy Resistance.International journal of molecular sciences · 2020Review
- Helping the Released Guardian: Drug Combinations for Supporting the Anticancer Activity of HDM2 (MDM2) Antagonists.Cancers · 2019Review
- HelixComplex snail mucus exhibits pro-survival, proliferative and pro-migration effects on mammalian fibroblasts.Scientific reports · 2018Article
- MDM2- and FLT3-inhibitors in the treatment ofHaematologica · 2018Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundBoth the multi-kinase inhibitor sorafenib and the small molecule inhibitor of the MDM2/p53 interaction, nutlin-3, used alone, have shown promising anti-leukemic activity in acute myeloid leukemia cells. Thus, in this study we investigated the effect of the combination of sorafenib plus nutlin-3 in acute myeloid leukemia. DESIGN AND
methodsPrimary acute myeloid leukemia blasts (n=13) and FLT3(wild-type)/p53(wild-type) (OCI-AML3), FLT3(mutated)/p53(wild-type) (MOLM), FLT3(mutated)/p53(mutated) (MV4-11), FLT3(wild-type)/p53(deleted) (HL60) or FLT3(wild-type)/p53(mutated) (NB4) acute myeloid cell lines were exposed to sorafenib, used alone or in association with nutlin-3 at a 1:1 ratio, in a range of clinically achievable concentrations (1-10 μM). Induction of apoptosis and autophagy was evaluated by transmission electron microscopy and by specific flow cytometry analyses. The levels of Mcl-1, p53 and Bak proteins were analyzed by western blotting. Knock-down of Bax and Bak gene expression was performed in transfection experiments with specific short interfering RNA.
resultsThe sorafenib+nutlin-3 drug combination exhibits synergistic cytotoxicity in primary acute myeloid leukemia blasts and in acute myeloid leukemia cell lines with maximal cytotoxicity in FLT3(mutated) MV4-11 and MOLM, followed by the FLT3(wild-type) OCI-AML3, HL60 and NB4 cell lines. The cytotoxic activity of sorafenib+nutlin-3 was characterized by an increase of both apoptosis and autophagy. Moreover, Bax and Bak showed prominent roles in mediating the decrease of cell viability in response to the drug combination in p53(wild-type) OCI-AML3 and p53(deleted) HL-60 cells, respectively, as demonstrated in transfection experiments performed with specific short interfering RNA.
conclusionsOur data demonstrate that acute myeloid leukemia cells show a variable but overall good susceptibility to the innovative therapeutic combination of sorafenib+nutlin-3, which differentially involves the pro-apoptotic Bcl-2 family members Bax and Bak in p53(wild-type) and p53(deleted) cells.
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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.