Inhibition of human transitional cell carcinoma in vitro proliferation by fluoroquinolone antibiotics.

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 micrograms./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 micrograms./ml., produced proliferation inhibition in the TCCSUP line ranging from 8.1% to 90.2% at 24 hours, 25.1% to 94.9% at 72 hours, and 53.8% to 96.9% at 120 hours. Inhibition of proliferation for the T24 line ranged from 8.0% to 85%, 31.5% to 96.5%, and 27.3% to 98.2%. Inhibition of proliferation of the J82 line ranged from 20.8% to 84.8%, 22.8% to 92.7%, and 37.4% to 97.1%. 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.