Inhibition of Human Transitional Cell Carcinoma in Vitro Proliferation by Fluoroquinolone Antibiotics

Abstract

Purpose The in vitro effects of the fluoroquinolone antibiotics ciprofloxacin and ofloxacin upon 3 human transitional cell carcinoma cell lines were investigated at concentrations that are attainable in the urine of patients taking these drugs orally. Materials and Methods Cell lines TCCSUP, T24, and J82 were exposed in culture to either ciprofloxacin or ofloxacin at concentrations ranging from 0 to 800 microgram/ml. and at durations ranging from 24 to 120 hours. Inhibition of proliferation and DNA synthesis were assessed via MTT and tritiated thymidine assays, respectively. Results From the MTT assay ciprofloxacin, at concentrations of 25 to 800 microgram/ml., produced proliferation inhibition in the TCCSUP line ranging from 8.1 percent to 90.2 percent at 24 hours, 25.1 percent to 94.9 percent at 72 hours, and 53.8 percent to 96.9 percent at 120 hours. Inhibition of proliferation for the T24 line ranged from 8.0 percent to 85 percent, 31.5 percent to 96.5 percent, and 27.3 percent to 98.2 percent. Inhibition of proliferation of the J82 line ranged from 20.8 percent to 84.8 percent, 22.8 percent to 92.7 percent, and 37.4 percent to 97.1 percent. Inhibition of DNA synthesis (due to ciprofloxacin at the concentrations above) as measured by the tritiated thymidine assay was also significant for each of the 3 cell lines. Inhibition of proliferation and DNA synthesis due to ofloxacin was lower but not overall statistically different from that due to ciprofloxacin. In a separate experiment, enhanced cytotoxicity was observed at lower concentrations of ciprofloxacin when the initial media pH was approximated to 5.5. Conclusions Ciprofloxacin and ofloxacin inhibit proliferation and DNA synthesis of these 3 human TCC lines in vitro. Inhibition occurred in a concentration- and time-dependent manner. The concentrations that were assessed are attainable in the urine of patients taking these agents orally.