Ciprofloxacin enhances phototoxicity of 5-aminolevulinic acid mediated photodynamic treatment for chordoma cell lines

Photodiagnosis Photodyn Ther. 2021 Sep:35:102346. doi: 10.1016/j.pdpdt.2021.102346. Epub 2021 May 24.

Abstract

Background: Chordoma are uncommon aggressive tumors of the skeleton. Surgical resection is often subtotal and adjuvant treatment possibilities are limited as chordomas are highly chemo- and radioresistant. In the present study we examined the impact of 5-ALA PDT on different human chordoma cell lines. Furthermore, we investigated the variation of two parameters: (1.) 5-ALA incubation time and (2.) supplemental use of ciprofloxacin as iron chelator.

Methods: Experiments were realized in vitro with three different human chordoma cell lines: U-CH2, U-CH2B and U-CH14. After pre-incubation for 24 h with various concentrations of ciprofloxacin (1.5 - 5.0 μg/ml), different amounts of 5-ALA (15 - 50 μg/ml) were applied to the cells either for a brief (4 h) or a long (6 h) incubation time. Subsequently cells were exposed to photodynamic radiation. Cell viability was exploited by WST-1 assay. Thus, for each of the three cell lines, two drug combinations (ciprofloxacin plus 5-ALA and 5-ALA only) and two incubation times (short, 4 h and long, 6 h) were tested. Negative control groups were also examined.

Results: Supplemental use of ciprofloxacin led to increased cell death in each of the cell lines. Different 5-ALA incubation times (4 h vs. 6 h) showed no significant differences in cell viability except for U-CH2.

Conclusion: Ciprofloxacin as an ordinary applied antibiotic, enhanced the effect of 5-ALA PDT on different human chordoma cell lines in vitro. The impact was dependent on the dose of ciprofloxacin-5-ALA. There were no notable differences for the tested 5-ALA incubation times. In human chordoma cell lines 5-ALA PDT may effectively be amended by ciprofloxacin.

Keywords: 5-ALA; 5-Amino levulinic acid; Chordoma; Ciprofloxacin; Iron chelator; Photo-dynamic therapy (PDT).

MeSH terms

  • Aminolevulinic Acid / pharmacology
  • Cell Line, Tumor
  • Cell Survival
  • Chordoma* / drug therapy
  • Ciprofloxacin / pharmacology
  • Humans
  • Photochemotherapy* / methods
  • Photosensitizing Agents / pharmacology

Substances

  • Photosensitizing Agents
  • Ciprofloxacin
  • Aminolevulinic Acid