ArticleScientific reports2016
Small molecule activation of NOTCH signaling inhibits acute myeloid leukemia.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 35 citations in OpenAlex.
- Translating molecular insights into clinical success: alkaloid-based therapies for leukemia.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Notch activator cyclopiazonic acid induces apoptosis in HL-60 cells through calcineurin activation.The Journal of antibiotics · 2024Article
- Exploring cell competition for the prevention and therapy of esophageal squamous cell carcinoma.Biochemical pharmacology · 2023Review
- Phytochemicals and bioactive compounds effective against acute myeloid leukemia: A systematic review.Food science & nutrition · 2023Article
- Notch signaling, hypoxia, and cancer.Frontiers in oncology · 2023Review
- Roles of transducin-like enhancer of split (TLE) family proteins in tumorigenesis and immune regulation.Frontiers in cell and developmental biology · 2022Review
- Characteristics of leukemic stem cells in acute leukemia and potential targeted therapies for their specific eradication.Cancer drug resistance (Alhambra, Calif.) · 2022Review
- Targeting Notch to Maximize Chemotherapeutic Benefits: Rationale, Advanced Strategies, and Future Perspectives.Cancers · 2021Review
- Model guided trait-specific co-expression network estimation as a new perspective for identifying molecular interactions and pathways.PLoS computational biology · 2021Article
- NOTCH and Esophageal Squamous Cell Carcinoma.Advances in experimental medicine and biology · 2021Review
- Advances in the Chemical and Biological Characterization of Amaryllidaceae Alkaloids and Natural Analogues Isolated in the Last Decade.Molecules (Basel, Switzerland) · 2020Review
- Investigating the inhibitory effect of miR-34a, miR-449a, miR-1827, and miR-106b on target genes including NOTCH1, c-Myc, and CCND1 in human T cell acute lymphoblastic leukemia clinical samples and cell line.Iranian journal of basic medical sciences · 2020Article
- Notch Signaling Orchestrates Helminth-Induced Type 2 Inflammation.Trends in immunology · 2019Review
- Antiproliferative and Immunoregulatory Effects of Azelaic Acid Against Acute Myeloid LeukemiaFrontiers in pharmacology · 2019Article
- Loss of Function of Canonical Notch Signaling Drives Head and Neck Carcinogenesis.Clinical cancer research : an official journal of the American Association for Cancer Research · 2018Article
- ZYH005, a novel DNA intercalator, overcomes all-trans retinoic acid resistance in acute promyelocytic leukemia.Nucleic acids research · 2018Article
- Knockdown of miR-128a induces Lin28a expression and reverts myeloid differentiation blockage in acute myeloid leukemia.Cell death & disease · 2017Article
- Novel agents for the treatment of childhood leukemia: an update.OncoTargets and therapy · 2017Review
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aberrant activation of the NOTCH signaling pathway is crucial for the onset and progression of T cell leukemia. Yet recent studies also suggest a tumor suppressive role of NOTCH signaling in acute myeloid leukemia (AML) and reactivation of this pathway offers an attractive opportunity for anti-AML therapies. N-methylhemeanthidine chloride (NMHC) is a novel Amaryllidaceae alkaloid that we previously isolated from Zephyranthes candida, exhibiting inhibitory activities in a variety of cancer cells, particularly those from AML. Here, we report NMHC not only selectively inhibits AML cell proliferation in vitro but also hampers tumor development in a human AML xenograft model. Genome-wide gene expression profiling reveals that NMHC activates the NOTCH signaling. Combination of NMHC and recombinant human NOTCH ligand DLL4 achieves a remarkable synergistic effect on NOTCH activation. Moreover, pre-inhibition of NOTCH by overexpression of dominant negative MAML alleviates NMHC-mediated cytotoxicity in AML. Further mechanistic analysis using structure-based molecular modeling as well as biochemical assays demonstrates that NMHC docks in the hydrophobic cavity within the NOTCH1 negative regulatory region (NRR), thus promoting NOTCH1 proteolytic cleavage. Our findings thus establish NMHC as a potential NOTCH agonist that holds great promises for future development as a novel agent beneficial to patients with AML.
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Registered trials
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