ArticleCancer letters2016
Hexamethylene amiloride engages a novel reactive oxygen species- and lysosome-dependent programmed necrotic mechanism to selectively target breast cancer cells.
Article in Cancer letters, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
23 citing papers in PubMed, 36 citations in OpenAlex.
- Targeting lysosome-dependent cell death in cancer: towards therapeutic strategies.Biomarker research · 2026Review
- NHE1-Mediated Metabolic Reprogramming in Cancer.Metabolites · 2026Review
- Development of a Novel Lysosomal Gene-based Prognostic Panel and Uncovering EIF4EBP1 as a Biomarker for Breast Cancer.Current genomics · 2025Article
- Hexamethylene amiloride induces lysosome-mediated cell death in multiple myeloma through transcription factor E3.Cell death discovery · 2024Article
- A novel lipophilic amiloride derivative efficiently kills chemoresistant breast cancer cells.Scientific reports · 2024Article
- Therapeutic strategies of targeting non-apoptotic regulated cell death (RCD) with small-molecule compounds in cancer.Acta pharmaceutica Sinica. B · 2024Review
- Ir(III) Half-Sandwich Photosensitizers with a π-Expansive Ligand for Efficient Anticancer Photodynamic Therapy.Journal of medicinal chemistry · 2024Article
- ISG15 mediates the function of extracellular vesicles in promoting ovarian cancer progression and metastasis.Journal of extracellular biology · 2024Article
- Review
- Article
- Therapeutic efficacy of proton transport inhibitors alone or in combination with cisplatin in triple negative and hormone sensitive breast cancer models.Cancer medicine · 2022Article
- Targeting the Interplay between Cancer Metabolic Reprogramming and Cell Death Pathways as a Viable Therapeutic Path.Biomedicines · 2021Review
- Transformable amyloid-beta mimetic peptide amphiphiles for lysosomal disruption in non-small cell lung cancer.Biomaterials · 2021Article
- Pyrazine ring-based NaScientific reports · 2020Article
- Repurposing Cationic Amphiphilic Drugs and Derivatives to Engage Lysosomal Cell Death in Cancer Treatment.Frontiers in oncology · 2020Review
- Hybrid Systems Based on Talc and Chitosan for Controlled Drug Release.Materials (Basel, Switzerland) · 2019Article
- A Syngeneic ErbB2 Mammary Cancer Model for Preclinical Immunotherapy Trials.Journal of mammary gland biology and neoplasia · 2019Article
- 6-Substituted Hexamethylene Amiloride (HMA) Derivatives as Potent and Selective Inhibitors of the Human Urokinase Plasminogen Activator for Use in Cancer.Journal of medicinal chemistry · 2018Article
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- Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Anticancer chemotherapeutics often rely on induction of apoptosis in rapidly dividing cells. While these treatment strategies are generally effective in debulking the primary tumor, post-therapeutic recurrence and metastasis are pervasive concerns with potentially devastating consequences. We demonstrate that the amiloride derivative 5-(N,N-hexamethylene) amiloride (HMA) harbors cytotoxic properties particularly attractive for a novel class of therapeutic agent. HMA is potently and specifically cytotoxic toward breast cancer cells, with remarkable selectivity for transformed cells relative to non-transformed or primary cells. Nonetheless, HMA is similarly cytotoxic to breast cancer cells irrespective of their molecular profile, proliferative status, or species of origin, suggesting that it engages a cell death mechanism common to all breast tumor subtypes. We observed that HMA induces a novel form of caspase- and autophagy-independent programmed necrosis relying on the orchestration of mitochondrial and lysosomal pro-death mechanisms, where its cytotoxicity was attenuated with ROS-scavengers or lysosomal cathepsin inhibition. Overall, our findings suggest HMA may efficiently target the heterogeneous populations of cancer cells known to reside within a single breast tumor by induction of a ROS- and lysosome-mediated form of programmed necrosis.
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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.