Scherzad Agmal, Hackenberg Stephan, Schramm Carolin, Froelich Katrin, Ginzkey Christian, Hagen Rudolf, Kleinsasser Norbert
Department of Otorhinolaryngology, Plastic, Aesthetic and Reconstructive Head and Neck Surgery, University of Wuerzburg, Josef-Schneider-Str. 11, D-97080 Wuerzburg, Germany.
Toxicol In Vitro. 2015 Jun;29(4):813-8. doi: 10.1016/j.tiv.2015.01.018. Epub 2015 Mar 10.
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.
沙利霉素通常应用于家畜养殖，但也被描述为一种有前景的抗癌干细胞（CSC）药物。然而，关于这种离子载体物质毒性的了解并不完整。本研究的目的是调查沙利霉素对人非恶性细胞的细胞毒性和遗传毒性作用。使用来自10名个体的原代人鼻黏膜细胞（单层和微型器官培养物）和外周血淋巴细胞，通过膜联蛋白-碘化丙啶和MTT试验研究沙利霉素（0.1 - 175μM）的细胞毒性作用。进行彗星试验以评估DNA损伤。此外，通过ELISA分析白细胞介素-8的分泌。流式细胞术和MTT试验显示，在10 - 20μM的低沙利霉素浓度下，鼻黏膜细胞和淋巴细胞有显著的细胞毒性作用。未观察到遗传毒性作用。在5μM时白细胞介素-8分泌升高。在与抗癌治疗相关的浓度下可观察到沙利霉素诱导的细胞毒性和促炎作用。在评估沙利霉素在实验肿瘤学中的应用时，需要监测并尽可能减少其对非恶性细胞的不良影响。还需要进一步研究以评估其在多种人类细胞系统中的毒性作用，例如肝、肾和肌肉细胞。
