ArticleMolecular cancer therapeutics2015
Direct binding of arsenic trioxide to AMPK and generation of inhibitory effects on acute myeloid leukemia precursors.
Article in Molecular cancer therapeutics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- Divergent Effects of Arsenic on NF-κB Signaling in Different Cells or Tissues: A Systematic Review and Meta-Analysis.International journal of environmental research and public health · 2016Pooled it
- Development of a Direct-to-Biology Platform to Discover Potent MNK Inhibitors.Journal of medicinal chemistry · 2026Article
- A Chemical-Genetic Interaction Matrix Reveals Drug Mechanism and Genetic Architecture.bioRxiv : the preprint server for biology · 2026Article
- Discovery of Potent and Selective MNK Kinase Inhibitors for the Treatment of Leukemia.Journal of medicinal chemistry · 2025Article
- Arsenic and Tau Phosphorylation: a Mechanistic Review.Biological trace element research · 2023Review
- The role of autophagy in metal-induced urogenital carcinogenesis.Seminars in cancer biology · 2021Review
- RSK Isoforms in Acute Myeloid Leukemia.Biomedicines · 2021Review
- Inhibitory effects of Tomivosertib in acute myeloid leukemia.Oncotarget · 2021Article
- Discovery of novel Mnk inhibitors using mutation-based induced-fit virtual high-throughput screening.Chemical biology & drug design · 2019Article
- Methylated metabolite of arsenite blocks glycerol production in yeast by inhibition of glycerol-3-phosphate dehydrogenase.Molecular biology of the cell · 2019Article
- Article
- Combination of ATO with FLT3 TKIs eliminates FLT3/ITD+ leukemia cells through reduced expression of FLT3.Oncotarget · 2018Article
- Differential Response of Glioma Stem Cells to Arsenic Trioxide Therapy Is Regulated by MNK1 and mRNA Translation.Molecular cancer research : MCR · 2018Article
- Artemisinin and Its Derivatives as a Repurposing Anticancer Agent: What Else Do We Need to Do?Molecules (Basel, Switzerland) · 2016Review
- Pre-clinical evidence of PIM kinase inhibitor activity in BCR-ABL1 unmutated and mutated Philadelphia chromosome-positive (Ph+) leukemias.Oncotarget · 2015Article
- Hyperoside enhances the suppressive effects of arsenic trioxide on acute myeloid leukemia cells.International journal of clinical and experimental medicine · 2015Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Arsenic trioxide (As2O3) exhibits potent antineoplastic effects and is used extensively in clinical oncology for the treatment of a subset of patients with acute myeloid leukemia (AML). Although As2O3 is known to regulate activation of several signaling cascades, the key events, accounting for its antileukemic properties, remain to be defined. We provide evidence that arsenic can directly bind to cysteine 299 in AMPKα and inhibit its activity. This inhibition of AMPK by arsenic is required in part for its cytotoxic effects on primitive leukemic progenitors from patients with AML, while concomitant treatment with an AMPK activator antagonizes in vivo the arsenic-induced antileukemic effects in a xenograft AML mouse model. A consequence of AMPK inhibition is activation of the mTOR pathway as a negative regulatory feedback loop. However, when AMPK expression is lost, arsenic-dependent activation of the kinase RSK downstream of MAPK activity compensates the generation of regulatory feedback signals through phosphorylation of downstream mTOR targets. Thus, therapeutic regimens with As2O3 will need to include inhibitors of both the mTOR and RSK pathways in combination to prevent engagement of negative feedback loops and maximize antineoplastic responses.
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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.