Ciprofloxacin and Levofloxacin as Potential Drugs in Genitourinary Cancer Treatment—The Effect of Dose–Response on 2D and 3D Cell Cultures

Abstract

Introduction: Introducing new drugs for clinical application is a very difficult, long, drawn-out, and costly process, which is why drug repositioning is increasingly gaining in importance. The aim of this study was to analyze the cytotoxic properties of ciprofloxacin and levofloxacin on bladder and prostate cell lines in vitro. Methods: Bladder and prostate cancer cell lines together with their non-malignant counterparts were used in this study. In order to evaluate the cytotoxic effect of both drugs on tested cell lines, MTT assay, real-time cell growth analysis, apoptosis detection, cell cycle changes, molecular analysis, and 3D cultures were examined. Results: Both fluoroquinolones exhibited a toxic effect on all of the tested cell lines. In the case of non-malignant cell lines, the cytotoxic effect was weaker, which was especially pronounced in the bladder cell line. A comparison of both fluoroquinolones showed the advantage of ciprofloxacin (lower doses of drug caused a stronger cytotoxic effect). Both fluoroquinolones led to an increase in late apoptotic cells and an inhibition of cell cycle mainly in the S phase. Molecular analysis showed changes in BAX, BCL2, TP53, and CDKN1 expression in tested cell lines following incubation with ciprofloxacin and levofloxacin. The downregulation of topoisomerase II genes (TOP2A and TOP2B) was noticed. Three-dimensional (3D) cell culture analysis confirmed the higher cytotoxic effect of tested fluoroquinolone against cancer cell lines. Conclusions: Our results suggest that both ciprofloxacin and levofloxacin may have great potential, especially in the supportive therapy of bladder cancer treatment. Taking into account the low costs of such therapy, fluoroquinolones seem to be ideal candidates for repositioning into bladder cancer therapeutics.

The Effect of Fatty Acids on Ciprofloxacin Cytotoxic Activity in Prostate Cancer Cell Lines—Does Lipid Component Enhance Anticancer Ciprofloxacin Potential?

“…The effect of ciprofloxacin used in high concentrations (about 200 µg/mL) on the bladder and prostate cancer cell lines has been demonstrated in in vitro studies [ 6 , 33 ]. In addition, a comparison of the cytotoxic action of ciprofloxacin and levofloxacin on prostate and bladder cancer indicated a greater anticancer potential of ciprofloxacin [ 34 ].…”

Quinolones as a Potential Drug in Genitourinary Cancer Treatment—A Literature Review

“…Additionally, we tested both drugs on a non-malignant uroepithelial cell line. Our results showed that both tested drugs were more effective against cancer cell lines which were more pronounced in 3D culture ( 62 ).…”

“…Levofloxacin, compared to ciprofloxacin, was more effective against the DU-145 cell line after a 24-h incubation, while after 48 h the situation was opposite. In this study, the advantage of both drugs over cancer cells was demonstrated ( 62 ). In the case of norfloxacin, it was shown that prostate cancer cells were the most resistant to this drug among all tested cancer cell lines.…”

“…Inhibition of topoisomerase led to the inhibition of DNA synthesis and its fragmentation. Downregulation of TOP2A and TOP2B genes, two isomers of topoisomerase II, were observed after ciprofloxacin and levofloxacin treatment ( 62 ). Quinolones induced cell death mainly through apoptosis, rarely necrosis ( 62 , 75 , 77 , 80 – 82 ).…”

“…Downregulation of TOP2A and TOP2B genes, two isomers of topoisomerase II, were observed after ciprofloxacin and levofloxacin treatment ( 62 ). Quinolones induced cell death mainly through apoptosis, rarely necrosis ( 62 , 75 , 77 , 80 – 82 ). Apoptosis was not observed after the use of gatifloxacin and moxifloxacin.…”