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.
Highlights
Introducing new drugs for clinical application is a very difficult, long, drawnout, 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
Levofloxacin belongs to the third generation of quinolones, it is an isoform of ofloxacin and has a complex ring connected to the oxazinoquinoline core [7]
Despite many therapeutic possibilities, including surgical methods accompanied by chemotherapy, radiotherapy, and immunotherapy, many deaths related to prostate and bladder cancers are still observed
Summary
Introducing new drugs for clinical application is a very difficult, long, drawnout, 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. They are divided into four groups; a fluoride atom was added to drug molecules in second quinolone group, leading to the formation of fluoroquinolones Their mechanism of action is based on an inhibition of bacterial gyrase [1,2]. They are very effective against Gram-negative bacteria and most of their representatives accumulates in urine and organs such as the prostate, reaching concentrations higher than in serum [3]. Ciprofloxacin belongs to the second generation of quinolones, in which the fluorine atom is attached to the C6 position of the quinolone scaffold Such a modification significantly increases drug penetration in bacterial cells, increases DNA gyrase inhibition (>10 fold), and is responsible for a wide range of drug activity [5,6]. Levofloxacin belongs to the third generation of quinolones, it is an isoform of ofloxacin and has a complex ring connected to the oxazinoquinoline core [7]
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