ArticleBiochemical pharmacology2015
Disulfiram-induced cytotoxicity and endo-lysosomal sequestration of zinc in breast cancer cells.
Article in Biochemical pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
28 citing papers in PubMed.
- Design and Development of Dry Powder Cyclodextrin Complexes of Zinc Diethyldithiocarbamate for Pulmonary Drug Delivery.Pharmaceutics · 2026Article
- Copper overload drives hepatic stellate cell activation via cuproptosis to exacerbate acute liver injury in murine malaria.Parasites & vectors · 2026Article
- Zinc as a master regulator of intracellular organelle homeostasis.Experimental & molecular medicine · 2026Review
- Crossroads of iron, copper, and zinc in cancer: a paradox of toxicity and therapy.Molecular biology reports · 2026Review
- Development and validation of a machine learning-driven mitochondrial gene signature for the diagnosis of breast cancer.Frontiers in immunology · 2025Article
- Comprehensive review of the repositioning of non-oncologic drugs for cancer immunotherapy.Medical oncology (Northwood, London, England) · 2024Review
- Review
- Preparation and Characterisation of Zinc Diethyldithiocarbamate-Cyclodextrin Inclusion Complexes for Potential Lung Cancer Treatment.Pharmaceutics · 2023Article
- Targeting Esophageal Squamous Cell Carcinoma by Combining Copper Ionophore Disulfiram and JMJD3/UTX Inhibitor GSK J4.Cancers · 2023Article
- Repurposing Disulfiram as an Antimicrobial Agent in Topical Infections.Antibiotics (Basel, Switzerland) · 2022Article
- USP21 promotes self-renewal and tumorigenicity of mesenchymal glioblastoma stem cells by deubiquitinating and stabilizing FOXD1.Cell death & disease · 2022Article
- Mouse pharmacokinetics and metabolism of the phenylurea thiocarbamate NSC 161128.Cancer chemotherapy and pharmacology · 2022Article
- Cytotoxic effect of disulfiram/copper on human cervical cancer cell lines and LGR5-positive cancer stem-like cells.BMC cancer · 2022Article
- Disulfiram/copper induces antitumor activity against gastric cancer cells in vitro and in vivo by inhibiting S6K1 and c-Myc.Cancer chemotherapy and pharmacology · 2022Article
- Comparative study of the effects of ziram and disulfiram on human monocyte-derived macrophage functions and polarization: involvement of zinc.Cell biology and toxicology · 2021Article
- The Role of Zinc and Copper in Gynecological Malignancies.Nutrients · 2020Review
- Targeting zinc metalloenzymes in coronavirus disease 2019.British journal of pharmacology · 2020Review
- Identification of novel activators of the metal responsive transcription factor (MTF-1) using a gene expression biomarker in a microarray compendium.Metallomics : integrated biometal science · 2020Article
- The biological activity of bispecific trastuzumab/pertuzumab plant biosimilars may be drastically boosted by disulfiram increasing formaldehyde accumulation in cancer cells.Scientific reports · 2019Article
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors.
Funding
Abstract
Disulfiram, a clinically used alcohol-deterrent has gained prominence as a potential anti-cancer agent due to its impact on copper-dependent processes. Few studies have investigated zinc effects on disulfiram action, despite it having high affinity for this metal. Here we studied the cytotoxic effects of disulfiram in breast cancer cells, and its relationship with both intra and extracellular zinc. MCF-7 and BT474 cancer cell lines gave a striking time-dependent biphasic cytotoxic response between 0.01 and 10 μM disulfiram. Co-incubation of disulfiram with low-level zinc removed this effect, suggesting that availability of extracellular zinc significantly influences disulfiram efficacy. Live-cell confocal microscopy using fluorescent endocytic probes and the zinc dye Fluozin-3 revealed that disulfiram selectively and rapidly increased zinc levels in endo-lysosomes. Disulfiram also caused spatial disorganization of late endosomes and lysosomes, suggesting they are novel targets for this drug. This relationship between disulfiram toxicity and ionophore activity was consolidated via synthesis of a new disulfiram analog and overall we demonstrate a novel mechanism of disulfiram-cytotoxicity with significant clinical implications for future use as a cancer therapeutic.
Indexed as
Identifiers
What OpenQuestion holds
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.