ArticleMedical oncology (Northwood, London, England)2015
MK-2206 induces apoptosis of AML cells and enhances the cytotoxicity of cytarabine.
Article in Medical oncology (Northwood, London, England), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
16 citing papers in PubMed, 23 citations in OpenAlex.
- Exploiting an epigenetic resistance mechanism to PI3-kinase inhibition in leukemic stem cells.Leukemia · 2026Article
- Machine learning-driven glycolytic subtyping and exosome-based PKM splicing modulation overcome drug resistance in hyper-glycolytic myeloid leukemia.NPJ digital medicine · 2025Article
- CN7:1h Alleviates Inflammation, Apoptosis and Extracellular Matrix Degradation in Osteoarthritis by Modulating the NF-κB and mTOR Pathways.Journal of cellular and molecular medicine · 2025Article
- Endoxifen downregulates AKT phosphorylation through protein kinase C beta 1 inhibition in ERα+ breast cancer.NPJ breast cancer · 2023Article
- Combination Therapies with Kinase Inhibitors for Acute Myeloid Leukemia Treatment.Hematology reports · 2023Review
- Pyrimidine-5-carbonitrile based potential anticancer agents as apoptosis inducers through PI3K/AKT axis inhibition in leukaemia K562.Journal of enzyme inhibition and medicinal chemistry · 2022Article
- Insilco and Invitro approaches identify novel dual PI3K/AKT pathway inhibitors to control acute myeloid leukemia cell proliferations.Medical oncology (Northwood, London, England) · 2022Article
- PI3K Targeting in Non-solid Cancer.Current topics in microbiology and immunology · 2022Review
- Anticancer efficacy of 3-(4-isopropyl) benzylidene-8-ethoxy, 6-methyl, chroman-4-one (SBL-060), a novel, dual, estrogen receptor-Akt kinase inhibitor in acute myeloid leukemia cells.Oncology research · 2021Article
- Targeting PI3K/Akt/mTOR in AML: Rationale and Clinical Evidence.Journal of clinical medicine · 2020Review
- LAM-003, a new drug for treatment of tyrosine kinase inhibitor-resistant FLT3-ITD-positive AML.Blood advances · 2019Article
- Allosteric AKT Inhibitors Target Synthetic Lethal Vulnerabilities in E-Cadherin-Deficient Cells.Cancers · 2019Article
- mTOR inhibitor Everolimus-induced apoptosis in melanoma cells.Journal of cell communication and signaling · 2019Article
- Dual blockade of the PI3K/Akt/mTOR pathway inhibits posttransplant Epstein-Barr virus B cell lymphomas and promotes allograft survival.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2019Article
- Cytarabine-ResistantInternational journal of molecular sciences · 2019Article
- Update on acute myeloid leukemia stem cells: New discoveries and therapeutic opportunities.World journal of stem cells · 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
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Genetic alterations in the PI3K/AKT cascade have been linked to various human cancers including acute myeloid leukemia (AML) and have emerged to be promising targets for treatment. In this study, we explored the molecular mechanism and clinical implication of a specific allosteric AKT inhibitor, MK-2206, in the treatment of AML. Four leukemia cell lines, MV-4-11, MOLM-13, OCI/AML3, and U937, were used. Apoptosis and cell cycle distribution were determined by flow cytometry analysis. Expression of anti-apoptotic protein family and glycogen synthase kinase 3β (GSK3β) signaling was determined by western blotting. Drug combination effects of MK-2206 with cytarabine were evaluated by cell proliferation assay, and the combination index values were calculated by CompuSyn software. MK-2206 had no effect on normal peripheral blood mononuclear cells, but induced G1-phase arrest and apoptosis in leukemia cells. Among anti-apoptotic Bcl-2 family members, only myeloid cell leukemia-1 (Mcl-1) was significantly suppressed. Mcl-1 suppression by MK-2206 was closely associated with decreased GSK3β phosphorylation at Ser9, an event leads to GSK3β activation. Furthermore, the effect of MK-2206 on Mcl-1 downregulation was abolished by GSK3β inhibitor, lithium chloride and proteasome inhibitor, MG-132, suggesting that MK-2206 acted through a GSK3β-mediated, proteasome-dependent protein degradation. In addition, co-administration of MK-2206 with cytarabine could enhance the cytotoxic efficacy of cytarabine in leukemia cell lines. In conclusion, we have demonstrated that MK-2206 is an active agent in AML and its efficacy as in combination with cytarabine is implicated.
Indexed as
Identifiers
What OpenQuestion holds
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.