The observed proteome changes, e.g. the significant down-regulation of the ETC complexes I and IV by Ciprofloxacin and Levofloxacin are in line with the literature-known mitochondrial toxicity of fluoroquinolones. However, Ciprofloxacin and Levofloxacin do not exert high general cytotoxicity as judged by the metabolic activity of HEK-293 and PDL-hTERT cells via MTT assays after 3 days of treatment with approximate apparent IC50 values well above the reported plasma concentrations (Figure ). Although FQs have been reported to induce apoptosis at levels exceeding the plasma and peak concentrations, our FACS-based cell-death assays using the standard 7.5 µM and 75 µM peak concentrations of Ciprofloxacin and Levofloxacin in PDL-hTERT cells for 3 days, did not reveal a significantly higher population of early-or late-stage apoptotic cells compared to control cells, although prolonged treatment for 7 days led to a rounded cell morphology (Figure ). We thus conclude that FQs do not exhibit acute cell toxicity and primarily a different mode of action must be responsible for the observed mitochondrial toxicity, which rather develops over a longer time of drug treatment and potentially accumulation.