ArticleMolecules (Basel, Switzerland)2020
Primary Human Hepatocytes, but Not HepG2 or Balb/c 3T3 Cells, Efficiently Metabolize Salinomycin and Are Resistant to Its Cytotoxicity.
Article in Molecules (Basel, Switzerland), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 9 citations in OpenAlex.
- Dacarbazine as a Positive Control in Melanoma Cell Lines (A375, SK-MEL-103, 1205Lu) and a Human Ex Vivo Skin Model.Advanced biology · 2026Article
- In Vitro and Ex Vivo Evaluation of Rifampicin Cytotoxicity in Human Skin Models.Antibiotics (Basel, Switzerland) · 2025Article
- Protective Action of Cannabidiol on Tiamulin Toxicity in Humans-In Vitro Study.International journal of molecular sciences · 2024Article
- Elucidating the role of S100A10 in CD8Cell death & disease · 2024Article
- Ionophore Toxicity in Animals: A Review of Clinical and Molecular Aspects.International journal of molecular sciences · 2023Review
- LC-HRMS-Based Identification of Transformation Products of the Drug Salinomycin Generated by Electrochemistry and Liver Microsome.Antibiotics (Basel, Switzerland) · 2022Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Salinomycin is a polyether antibiotic showing anticancer activity. There are many reports of its toxicity to animals but little is known about the potential adverse effects in humans. The action of the drug may be connected to its metabolism. That is why we investigated the cytotoxicity of salinomycin and pathways of its biotransformation using human primary hepatocytes, human hepatoma cells (HepG2), and the mouse fibroblast cell line (Balb/c 3T3). The cytotoxicity of salinomycin was time-dependent, concentration-dependent, and cell-dependent with primary hepatocytes being the most resistant. Among the studied models, primary hepatocytes were the only ones to efficiently metabolize salinomycin but even they were saturated at higher concentrations. The main route of biotransformation was monooxygenation leading to the formation of monohydroxysalinomycin, dihydroxysalinomycin, and trihydroxysalinomycin. Tiamulin, which is a known inhibitor of CYP450 izoenzymes, synergistically induced cytotoxicity of salinomycin in all cell types, including non-metabolising fibroblasts. Therefore, the pharmacokinetic interaction cannot fully explain tiamulin impact on salinomycin toxicity.
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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.