title: Geno- and cytotoxicity of salinomycin in human nasal mucosa and peripheral blood lymphocytes.
abstract: Salinomycin is usually applied in stock breading but has also been described as a promising agent against cancer stem cells (CSC). However, knowledge about the toxicity of this ionophor substance is incomplete. The aim of this study was to investigate cyto- and genotoxic effects of salinomycin in human non-malignant cells. Primary human nasal mucosa cells (monolayer and mini organ cultures) and peripheral blood lymphocytes from 10 individuals were used to study the cytotoxic effects of salinomycin (0.1-175 μM) by annexin-propidiumiodide- and MTT-test. The comet assay was performed to evaluate DNA damage. Additionally, the secretion of interleukin-8 was analyzed by ELISA. Flow cytometry and MTT assay revealed significant cytotoxic effects in nasal mucosa cells and lymphocytes at low salinomycin concentrations of 10-20 μM. No genotoxic effects could be observed. IL-8 secretion was elevated at 5 μM. Salinomycin-induced cytotoxic and pro-inflammatory effects were seen at concentrations relevant for anti-cancer treatment. Concurrent to the evaluation of salinomycin application in experimental oncology, adverse effects in non-malignant cells need to be monitored and reduced as much as possible. Further studies are also warranted to evaluate the toxic effects in a variety of human cell systems, e.g., liver, kidney and muscle cells.
authors.affiliation: Department of Otorhinolaryngology, Plastic, Aesthetic and Reconstructive Head and Neck Surgery, University of Wuerzburg, Josef-Schneider-Str. 11, D-97080 Wuerzburg, Germany. Electronic address: scherzad_a@ukw.de.
authors.forename: Agmal
authors.initials: A
authors.lastname: Scherzad
authors.affiliation: Department of Otorhinolaryngology, Plastic, Aesthetic and Reconstructive Head and Neck Surgery, University of Wuerzburg, Josef-Schneider-Str. 11, D-97080 Wuerzburg, Germany. Electronic address: hackenberg_s@ukw.de.
authors.forename: Stephan
authors.initials: S
authors.lastname: Hackenberg
authors.affiliation: Department of Otorhinolaryngology, Plastic, Aesthetic and Reconstructive Head and Neck Surgery, University of Wuerzburg, Josef-Schneider-Str. 11, D-97080 Wuerzburg, Germany. Electronic address: carolin.schr@freenet.de.
authors.forename: Carolin
authors.initials: C
authors.lastname: Schramm
authors.affiliation: Department of Otorhinolaryngology, Plastic, Aesthetic and Reconstructive Head and Neck Surgery, University of Wuerzburg, Josef-Schneider-Str. 11, D-97080 Wuerzburg, Germany. Electronic address: froelich_k@ukw.de.
authors.forename: Katrin
authors.initials: K
authors.lastname: Froelich
authors.affiliation: Department of Otorhinolaryngology, Plastic, Aesthetic and Reconstructive Head and Neck Surgery, University of Wuerzburg, Josef-Schneider-Str. 11, D-97080 Wuerzburg, Germany. Electronic address: ginzkey_c@ukw.de.
authors.forename: Christian
authors.initials: C
authors.lastname: Ginzkey
authors.affiliation: Department of Otorhinolaryngology, Plastic, Aesthetic and Reconstructive Head and Neck Surgery, University of Wuerzburg, Josef-Schneider-Str. 11, D-97080 Wuerzburg, Germany. Electronic address: hagen_r@ukw.de.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Hagen
authors.affiliation: Department of Otorhinolaryngology, Plastic, Aesthetic and Reconstructive Head and Neck Surgery, University of Wuerzburg, Josef-Schneider-Str. 11, D-97080 Wuerzburg, Germany. Electronic address: kleinsasser_n@ukw.de.
authors.forename: Norbert
authors.initials: N
authors.lastname: Kleinsasser
mesh_terms: D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D002469:Cell Separation; D002470:Cell Survival / Q000187:drug effects*; D020552:Comet Assay; D005260:Female; D006801:Humans; D016209:Interleukin-8; D008214:Lymphocytes / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D009153:Mutagens / Q000633:toxicity*; D009297:Nasal Mucosa / Q000166:cytology* / Q000187:drug effects; D061251:Primary Cell Culture; D011714:Pyrans / Q000633:toxicity*; D012997:Solvents; D055815:Young Adult; D000095662:Polyether Polyketides
chemical_list: D000903:Antibiotics, Antineoplastic; D016209:Interleukin-8; D009153:Mutagens; D011714:Pyrans; D012997:Solvents; C508606:CXCL8 protein, human; C010327:salinomycin; D000095662:Polyether Polyketides
keywords: Genotoxicity; Lymphocytes; Nasal mucosa; Salinomycin; Toxicity