The established urinary
antibiotic nitroxoline has recently regained considerable attention, due to its potent activities in inhibiting angiogenesis, inducing apoptosis and blocking
cancer cell invasion. These features make
nitroxoline an excellent candidate for anticancer
drug repurposing. To rapidly advance
nitroxoline repurposing into clinical trials, the present study performed systemic preclinical pharmacodynamic evaluation of its anticancer activity, including a methyl thiazolyl tetrazolium assay in vitro and an orthotopic urological
tumor assay in vivo. The current study determined that
nitroxoline exhibits dose-dependent anti-
cancer activity in vitro and in urological
tumor orthotopic mouse models. In addition, it was demonstrated that the routine
nitroxoline administration regimen used for
urinary tract infections was effective and sufficient for
urological cancer treatment, and 2 to 4-fold higher doses resulted in obvious enhancement of anticancer efficacy without corresponding increases in toxicity. Furthermore,
nitroxoline sulfate, one of the most common metabolites of
nitroxoline in the urine, effectively inhibited
cancer cell proliferation. This finding increases the feasibility of
nitroxoline repurposing for
urological cancer treatment. Due to the excellent anticancer activity demonstrated in the present study, and its well-known safety profile and pharmacokinetic properties,
nitroxoline has been approved to enter into a phase II clinical trial in China for
non-muscle invasive bladder cancer treatment (registration no. CTR20131716).