ArticlePloS one2014
Inhibition of mTOR-dependent autophagy sensitizes leukemic cells to cytarabine-induced apoptotic death.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
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Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 66 citations in OpenAlex.
- A comprehensive analysis of the role of QPRT in breast cancer.Scientific reports · 2023Pooled it
- Mitophagy-driven prognosis in pediatric acute myeloid leukemia: a new frontier.Scientific reports · 2026Article
- The crosstalk between MiRNAs and autophagy in leukemia: mechanisms and therapeutic insights.Discover oncology · 2025Review
- Crosstalk Between Autophagy and Oxidative Stress in Hematological Malignancies: Mechanisms, Implications, and Therapeutic Potential.Antioxidants (Basel, Switzerland) · 2025Review
- High Mitophagy and Low Glycolysis Predict Better Clinical Outcomes in Acute Myeloid Leukemias.International journal of molecular sciences · 2024Article
- Enhancing Therapeutic Efficacy in Cancer Treatment: Integrating Nanomedicine with Autophagy Inhibition Strategies.ACS omega · 2024Review
- Progress in the study of autophagy-related proteins affecting resistance to chemotherapeutic drugs in leukemia.Frontiers in cell and developmental biology · 2024Review
- Folate-Appended Hydroxypropyl-β-Cyclodextrin Induces Autophagic Cell Death in Acute Myeloid Leukemia Cells.International journal of molecular sciences · 2023Article
- Galectin-9 has non-apoptotic cytotoxic activity toward acute myeloid leukemia independent of cytarabine resistance.Cell death discovery · 2023Article
- Autophagy: A challengeable paradox in cancer treatment.Cancer medicine · 2023Review
- The Question of Survival or Death: What Is the Role of Autophagy in Acute Myeloid Leukemia (AML)?International journal of hematology-oncology and stem cell research · 2022Review
- Role of Roflumilast Combined with ESHAP Chemotherapy in Relapsed/Refractory Patients with Diffuse Large B-Cell Lymphoma.Cancer research and treatment · 2022Article
- Acceleration of slow autophagy flux induced by arabinofuranosyl cytidine improves its antileukemic effectiveness in M-NFS-60 cells.Turkish journal of biology = Turk biyoloji dergisi · 2022Article
- Article
- Autophagy a Close Relative of AML Biology.Biology · 2021Review
- Mitochondrial metabolism as a target for acute myeloid leukemia treatment.Cancer & metabolism · 2021Review
- Long noncoding RNA DANCR confers cytarabine resistance in acute myeloid leukemia by activating autophagy via the miR-874-3P/ATG16L1 axis.Molecular oncology · 2021Article
- Inhibition of Autophagy Does Not Re-Sensitize Acute Myeloid Leukemia Cells Resistant to Cytarabine.International journal of molecular sciences · 2021Article
- Review
- Article
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The present study investigated the role of autophagy, a cellular self-digestion process, in the cytotoxicity of antileukemic drug cytarabine towards human leukemic cell lines (REH, HL-60, MOLT-4) and peripheral blood mononuclear cells from leukemic patients. The induction of autophagy was confirmed by acridine orange staining of intracellular acidic vesicles, electron microscopy visualization of autophagic vacuoles, as well as by the increase in autophagic proteolysis and autophagic flux, demonstrated by immunoblot analysis of p62 downregulation and LC3-I conversion to autophagosome-associated LC3-II in the presence of proteolysis inhibitors, respectively. Moreover, the expression of autophagy-related genes Atg4, Atg5 and Atg7 was stimulated by cytarabine in REH cells. Cytarabine reduced the phosphorylation of the major negative regulator of autophagy, mammalian target of rapamycin (mTOR), and its downstream target p70S6 kinase in REH cells, which was associated with downregulation of mTOR activator Akt and activation of extracellular signal- regulated kinase. Cytarabine had no effect on the activation of mTOR inhibitor AMP-activated protein kinase. Leucine, an mTOR activator, reduced both cytarabine-induced autophagy and cytotoxicity. Accordingly, pharmacological downregulation of autophagy with bafilomycin A1 and chloroquine, or RNA interference-mediated knockdown of LC3β or p62, markedly increased oxidative stress, mitochondrial depolarization, caspase activation and subsequent DNA fragmentation and apoptotic death in cytarabine-treated REH cells. Cytarabine also induced mTOR-dependent cytoprotective autophagy in HL-60 and MOLT-4 leukemic cell lines, as well as primary leukemic cells, but not normal leukocytes. These data suggest that the therapeutic efficiency of cytarabine in leukemic patients could be increased by the inhibition of the mTOR-dependent autophagic response.
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