ArticleGynecologic oncology2018
Evaluating class III antiarrhythmic agents as novel MYC targeting drugs in ovarian cancer.
Article in Gynecologic oncology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 14 citations in OpenAlex.
- Repurposing dronedarone induces ferroptosis through GPX4 inactivation and degradation in pancreatic cancer.Journal of experimental & clinical cancer research : CR · 2026Article
- Pan-cancer Myc modulator that targets Myc-α-tubulin interaction to drive selective mitotic catastrophe.Scientific reports · 2025Article
- Dronedarone inhibits the proliferation of esophageal squamous cell carcinoma through the CDK4/CDK6-RB1 axis in vitro and in vivo.Frontiers of medicine · 2024Article
- Microfluidic production of amiodarone loaded nanoparticles and application in drug repositioning in ovarian cancer.Scientific reports · 2024Article
- Drug repositioning and ovarian cancer, a study based on Mendelian randomisation analysis.Frontiers in oncology · 2024Article
- Gut-microbiota-microglia-brain interactions in Alzheimer's disease: knowledge-based, multi-dimensional characterization.Alzheimer's research & therapy · 2021Article
- Dronedarone blockage of the tumor-related Kv10.1 channel: a comparison with amiodarone.Pflugers Archiv : European journal of physiology · 2020Article
- Data-driven multiple-level analysis of gut-microbiome-immune-joint interactions in rheumatoid arthritis.BMC genomics · 2019Article
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Authors and funding
6 authors at 5 institutions in 1 country.
Funding
Abstract
objectiveTo evaluate the utility of amiodarone and its derivative dronedarone as novel drug repositioning candidates in EOC and to determine the potential pathways targeted by these drugs.
methodsDrug-predict bioinformatics platform was used to assess the utility of amiodarone as a novel drug-repurposing candidate in EOC. EOC cells were treated with amiodarone and dronedarone. Cell death was assessed by Annexin V staining. Cell viability and cell survival were assessed by MTT and clonogenics assays respectively. c-MYC and mTOR/Akt axis were evaluated as potential targets. Effect on autophagy was determined by autophagy flux flow cytometry.
results"DrugPredict" bioinformatics platform ranked Class III antiarrhythmic drug amiodarone within the top 3.9% of potential EOC drug repositioning candidates which was comparable to carboplatin ranking in the top 3.7%. Amiodarone and dronedarone were the only Class III antiarrhythmic drugs that decreased the cellular survival of both cisplatin-sensitive and cisplatin-resistant primary EOC cells. Interestingly, both drugs induced degradation of c-MYC protein and decreased the expression of known transcriptional targets of c-MYC. Furthermore, stable overexpression of non-degradable c-MYC partially rescued the effects of amiodarone and dronedarone induced cell death. Dronedarone induced higher autophagy flux in EOC cells as compared to amiodarone with decreased phospho-AKT and phospho-4EBP1 protein expression, suggesting autophagy induction due to inhibition of AKT/mTOR axis with these drugs. Lastly, both drugs also inhibited the survival of EOC tumor-initiating cells (TICs).
conclusionsWe provide the first evidence of class III antiarrhythmic agents as novel c-MYC targeting drugs and autophagy inducers in EOC. Since c-MYC is amplified in >40% ovarian tumors, our results provide the basis for repositioning amiodarone and dronedarone as novel c-MYC targeting drugs in EOC with potential extension to other cancers.
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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.