ArticlePloS one2014
Disulfiram suppresses growth of the malignant pleural mesothelioma cells in part by inducing apoptosis.
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 20 papers, 1 of them a synthesis that pooled it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.
- Anticancer effects of disulfiram: a systematic review of in vitro, animal, and human studies.Systematic reviews · 2022Pooled it
- Tumor specific in situ synthesis of therapeutic agent for precision cancer therapy.Journal of nanobiotechnology · 2024Article
- Combination of the cuproptosis inducer disulfiram and anti‑PD‑L1 abolishes NSCLC resistance by ATP7B to regulate the HIF‑1 signaling pathway.International journal of molecular medicine · 2024Article
- Advancing Cancer Therapy with Copper/Disulfiram Nanomedicines and Drug Delivery Systems.Pharmaceutics · 2023Review
- The ionophore thiomaltol induces rapid lysosomal accumulation of copper and apoptosis in melanoma.Metallomics : integrated biometal science · 2022Article
- Trace element levels in pleural effusions.Health science reports · 2021Article
- The radioenhancement potential of Schiff base derived copper (II) compounds against lung carcinoma in vitro.PloS one · 2021Article
- Review
- Disulfiram (Antabuse) Activates ROS-Dependent ER Stress and Apoptosis in Oral Cavity Squamous Cell Carcinoma.Journal of clinical medicine · 2019Article
- Podoplanin: An emerging cancer biomarker and therapeutic target.Cancer science · 2018Review
- Drug repurposing in malignant pleural mesothelioma: a breath of fresh air?European respiratory review : an official journal of the European Respiratory Society · 2018Review
- Recent Advances in Antabuse (Disulfiram): The Importance of its Metal-binding Ability to its Anticancer Activity.Current medicinal chemistry · 2018Review
- Telmisartan Induces Osteosarcoma Cells Growth Inhibition and Apoptosis Via Suppressing mTOR Pathway.Open life sciences · 2018Article
- Targeting the cancer stem cell marker, aldehyde dehydrogenase 1, to circumvent cisplatin resistance in NSCLC.Oncotarget · 2017Article
- Disulfiram-loaded porous PLGA microparticle for inhibiting the proliferation and migration of non-small-cell lung cancer.International journal of nanomedicine · 2017Article
- Elevation of Kynurenine Metabolites in Rat Liver and Serum: A Potential Additional Mechanism of the Alcohol Aversive and Anti-cancer Effects of Disulfiram?Alcohol and alcoholism (Oxford, Oxfordshire) · 2016Article
- PKA and CDK5 can phosphorylate specific serines on the intracellular domain of podoplanin (PDPN) to inhibit cell motility.Experimental cell research · 2015Article
- Eucommia ulmoides Oliv. (Du-Zhong) Lignans Inhibit Angiotensin II-Stimulated Proliferation by Affecting P21, P27, and Bax Expression in Rat Mesangial Cells.Evidence-based complementary and alternative medicine : eCAM · 2015Article
- Repurposing Drugs in Oncology (ReDO)-itraconazole as an anti-cancer agent.Ecancermedicalscience · 2015Article
- Article
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 2 countries.
Funding
Abstract
Dithiocarbamate compound Disulfiram (DSF) that binds with copper and functions as an inhibitor of aldehyde dehydrogenase is a Food and Drug Administration approved agent for treatment of alcoholism. Copper complexed DSF (DSF-Cu) also possesses anti-tumor and chemosensitizing properties; however, its molecular mechanisms of action remain unclear. Here we investigated malignant pleural mesothelioma (MPM) suppressive effects of DSF-Cu and the molecular mechanisms involved. DSF-Cu inhibited growth of the murine as well as human MPM cells in part by increasing levels of ubiquitinated proteins. DSF-Cu exposure stimulated apoptosis in MPM cells that involved activation of stress-activated protein kinases (SAPKs) p38 and JNK1/2, caspase-3, and cleavage of poly-(ADP-ribose)-polymerase, as well as increased expression of sulfatase 1 and apoptosis transducing CARP-1/CCAR1 protein. Gene-array based analyses revealed that DSF-Cu suppressed cell growth and metastasis-promoting genes including matrix metallopeptidase 3 and 10. DSF inhibited MPM cell growth and survival by upregulating cell cycle inhibitor p27Kip1, IGFBP7, and inhibitors of NF-κB such as ABIN 1 and 2 and Inhibitory κB (IκB)α and β proteins. DSF-Cu promoted cleavage of vimentin, as well as serine-phosphorylation and lysine-63 linked ubiquitination of podoplanin. Administration of 50 mg/kg DSF-Cu by daily i.p injections inhibited growth of murine MPM cell-derived tumors in vivo. Although podoplanin expression often correlates with metastatic disease and poor prognosis, phosphorylation of serines in cytoplasmic domain of podoplanin has recently been shown to interfere with cellular motility and migration signaling. Post-translational modification of podoplanin and cleavage of vimentin by DSF-Cu underscore a metastasis inhibitory property of this agent and together with our in vivo studies underscore its potential as an anti-MPM agent.
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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.