ArticleLeukemia2008
Blockade of mTOR signaling potentiates the ability of histone deacetylase inhibitor to induce growth arrest and differentiation of acute myelogenous leukemia cells.
Article in Leukemia, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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The trial behind it
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Who cites it
42 citing papers in PubMed, 85 citations in OpenAlex.
- The isothiocyanate sulforaphane inhibits mTOR in an NRF2-independent manner.Phytomedicine : international journal of phytotherapy and phytopharmacology · 2021Article
- Targeting PI3K/Akt/mTOR in AML: Rationale and Clinical Evidence.Journal of clinical medicine · 2020Review
- NTAL is associated with treatment outcome, cell proliferation and differentiation in acute promyelocytic leukemia.Scientific reports · 2020Article
- Metabolomics Reveals that Cysteine Metabolism Plays a Role in Celastrol-Induced Mitochondrial Apoptosis in HL-60 and NB-4 Cells.Scientific reports · 2020Article
- Berberine Induces Autophagic Cell Death in Acute Lymphoblastic Leukemia by Inactivating AKT/mTORC1 Signaling.Drug design, development and therapy · 2020Article
- HDAC Inhibitors in Acute Myeloid Leukemia.Cancers · 2019Review
- Intersection of Epigenetic and Metabolic Regulation of Histone Modifications in Acute Myeloid Leukemia.Frontiers in oncology · 2019Review
- LRRC25 plays a key role in all-trans retinoic acid-induced granulocytic differentiation as a novel potential leukocyte differentiation antigen.Protein & cell · 2018Article
- Bufalin induces apoptosis in human esophageal carcinoma ECA109 cells by inhibiting the activation of the mTOR/p70S6K pathway.Oncology letters · 2018Article
- Synergistic effects of phenylhexyl isothiocyanate and LY294002 on the PI3K/Akt signaling pathway in HL-60 cells.Oncology letters · 2017Article
- The mTOR inhibitor everolimus in combination with azacitidine in patients with relapsed/refractory acute myeloid leukemia: a phase Ib/II study.Oncotarget · 2017Article
- PLSCR1/IP3R1/CaCell death & disease · 2017Article
- Review
- Anti-CD44 antibodies inhibit both mTORC1 and mTORC2: a new rationale supporting CD44-induced AML differentiation therapy.Leukemia · 2016Article
- Trichostatin A Enhances the Apoptotic Potential of Palladium Nanoparticles in Human Cervical Cancer Cells.International journal of molecular sciences · 2016Article
- Article
- Co-targeting of Bcl-2 and mTOR pathway triggers synergistic apoptosis in BH3 mimetics resistant acute lymphoblastic leukemia.Oncotarget · 2015Article
- [Everolimus combined with all-trans retinoid acid reverses drug resistance in acute promyelocytic leukemia NB4-R1 cells].Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2015Article
- Histone acetyltransferases and histone deacetylases in B- and T-cell development, physiology and malignancy.Genes & cancer · 2015Review
- Novel oral histone deacetylase inhibitor, MPT0E028, displays potent growth-inhibitory activity against human B-cell lymphoma in vitro and in vivo.Oncotarget · 2015Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
This study found that MS-275, a novel synthetic benzamide histone deacetylase inhibitor (HDACI), blocked Akt/mammalian target of rapamycin (mTOR) signaling in acute myelogenous leukemia (AML) HL60 and acute promyelocytic leukemia (APL) NB4 cells, as assessed by decreased levels of the phosphorylated (p)-Akt, p-p70 ribosomal S6 kinase (p70S6K) and p-S6K by western blot analysis. Interestingly, further inactivation of mTOR by rapamycin analog RAD001 (everolimus) significantly enhanced MS-275-mediated growth inhibition and apoptosis of these cells in parallel with enhanced upregulation of p27(kip1) and downregulation of c-Myc. In addition, RAD001 potentiated the ability of MS-275 to induce differentiation of HL60 and NB4 cells, as measured by the expression of CD11b cell surface antigens, as well as reduction of nitroblue tetrazolium. Importantly, RAD001 potentiated the ability of MS-275 to induce the expression of the myeloid differentiation-related transcription factor, CCAAT enhancer-binding protein-epsilon, in these cells in association with enhanced acetylation of histone H3 on its promoter. Furthermore, RAD001 (5 mg/kg) significantly enhanced the effects of MS-275 (10 mg/kg) to inhibit proliferation of HL60 tumor xenografts in nude mice without adverse effects. Taken together, concomitant administration of an HDACI and an mTOR inhibitor may be a promising treatment strategy for the individuals with a subset of human leukemia.
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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.