ArticleEBioMedicine2019
Dual lysosomal-mitochondrial targeting by antihistamines to eradicate leukaemic cells.
Article in EBioMedicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 24 citations in OpenAlex.
- Targeting Lysosomes for Enhanced Anti-Cancer Therapeutics and Immune Response.International journal of biological sciences · 2026Review
- Review
- Lysosome targeted therapies in hematological malignancies.Frontiers in oncology · 2025Review
- Multi-omics and pharmacological characterization of patient-derived glioma cell lines.Nature communications · 2024Article
- Article
- Lysosomes as a Target of Anticancer Therapy.International journal of molecular sciences · 2023Review
- The Multidirectional Effect of Azelastine Hydrochloride on Cervical Cancer Cells.International journal of molecular sciences · 2022Article
- The dual role of autophagy in acute myeloid leukemia.Journal of hematology & oncology · 2022Review
- Lysosomes in Stem Cell Quiescence: A Potential Therapeutic Target in Acute Myeloid Leukemia.Cancers · 2022Review
- Lysosome-mediated chemoresistance in acute myeloid leukemia.Cancer drug resistance (Alhambra, Calif.) · 2022Review
- Review
- Insights into the molecular profiles of adult and paediatric acute myeloid leukaemia.Molecular oncology · 2021Review
- Histamine receptor 1 is expressed in leukaemic cells and affects differentiation sensitivity.Journal of cellular and molecular medicine · 2020Article
- Cationic amphiphilic drugs induce elevation in lysoglycerophospholipid levels and cell death in leukemia cells.Metabolomics : Official journal of the Metabolomic Society · 2020Article
- [Are cationic amphiphilic H1 antihistamines useful as adjuvant treatment of malignant melanoma?]Der Hautarzt; Zeitschrift fur Dermatologie, Venerologie, und verwandte Gebiete · 2020Article
- Review
- The emergence of antihistamines as unexpected allies in our fight against acute myeloid leukaemia.EBioMedicine · 2019Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDespite great efforts to identify druggable molecular targets for AML, there remains an unmet need for more effective therapies.
methodsAn in silico screening was performed using Connectivity Maps to identify FDA-approved drugs that may revert an early leukaemic transformation gene signature. Hit compounds were validated in AML cell lines. Cytotoxic effects were assessed both in primary AML patient samples and healthy donor blood cells. Xenotransplantation assays were undertaken to determine the effect on engraftment of hit compounds. The mechanism of action responsible for the antileukaemic effect was studied focussing on lysosomes and mitochondria.
findingsWe identified a group of antihistamines (termed ANHAs) with distinct physicochemical properties associated with their cationic-amphiphilic nature, that selectively killed leukaemic cells. ANHAs behaved as antileukaemic agents against primary AML samples ex vivo, sparing healthy cells. Moreover, ANHAs severely impaired the in vivo leukaemia regeneration capacity. ANHAs' cytotoxicity relied on simultaneous mitochondrial and lysosomal disruption and induction of autophagy and apoptosis. The pharmacological effect was exerted based on their physicochemical properties that permitted the passive targeting of both organelles, without the involvement of active molecular recognition.
interpretationDual targeting of lysosomes and mitochondria constitutes a new promising therapeutic approach for leukaemia treatment, supporting the further clinical development. FUND: This work was funded by the Fundación Mutua Madrileña (RMR), CaixaImpulse (RMR), the Spanish Ministry of Economy (RMR), the Josep Carreras International Leukaemia Foundation (RMR), l'Obra Social "La Caixa" (RMR), and Generalitat de Catalunya (IJC).
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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.