2. Academic Validation
  3. Lomefloxacin Induces Oxidative Stress and Apoptosis in COLO829 Melanoma Cells

Lomefloxacin Induces Oxidative Stress and Apoptosis in COLO829 Melanoma Cells

  • Int J Mol Sci. 2017 Oct 20;18(10):2194. doi: 10.3390/ijms18102194.
Artur Beberok 1,  Dorota Wrześniok 2,  Martyna Szlachta 3,  Jakub Rok 4,  Zuzanna Rzepka 5,  Michalina Respondek 6,  Ewa Buszman 7
Affiliations

Affiliations

  • 1 Department of Pharmaceutical Chemistry, School of Pharmacy with the Division of Laboratory Medicine, Medical University of Silesia, Jagiellońska 4, 41-200 Sosnowiec, Poland. abeberok@sum.edu.pl.
  • 2 Department of Pharmaceutical Chemistry, School of Pharmacy with the Division of Laboratory Medicine, Medical University of Silesia, Jagiellońska 4, 41-200 Sosnowiec, Poland. dwrzesniok@sum.edu.pl.
  • 3 Department of Pharmaceutical Chemistry, School of Pharmacy with the Division of Laboratory Medicine, Medical University of Silesia, Jagiellońska 4, 41-200 Sosnowiec, Poland. szlachta.martyna@gmail.com.
  • 4 Department of Pharmaceutical Chemistry, School of Pharmacy with the Division of Laboratory Medicine, Medical University of Silesia, Jagiellońska 4, 41-200 Sosnowiec, Poland. jrok@sum.edu.pl.
  • 5 Department of Pharmaceutical Chemistry, School of Pharmacy with the Division of Laboratory Medicine, Medical University of Silesia, Jagiellońska 4, 41-200 Sosnowiec, Poland. zuzarzepka@gmail.com.
  • 6 Department of Pharmaceutical Chemistry, School of Pharmacy with the Division of Laboratory Medicine, Medical University of Silesia, Jagiellońska 4, 41-200 Sosnowiec, Poland. michalina.respondek@med.sum.edu.pl.
  • 7 Department of Pharmaceutical Chemistry, School of Pharmacy with the Division of Laboratory Medicine, Medical University of Silesia, Jagiellońska 4, 41-200 Sosnowiec, Poland. ebuszman@sum.edu.pl.
PMID: 29053584 DOI: 10.3390/ijms18102194
Abstract

Although some fluoroquinolones have been found to exert anti-tumor activity, studies on the effect of these drugs on melanoma cells are relatively rare. The aim of this study was to examine the effect of lomefloxacin on cell viability, Reactive Oxygen Species production, redox balance, cell cycle distribution, DNA fragmentation, and Apoptosis in COLO829 melanoma cells. Lomefloxacin decreases the cell viability in a dose- and time-dependent manner. For COLO829 cells treated with the drug for 24, 48, and 72 h, the values of IC50 were found to be 0.51, 0.33, and 0.25 mmol/L, respectively. The analyzed drug also altered the redox signaling pathways, as shown by intracellular Reactive Oxygen Species overproduction and endogeneous glutathione depletion. After lomefloxacin treatment, the cells were arrested in S- and G2/M-phase, suggesting a mechanism related to Topoisomerase II inhibition. DNA fragmentation was observed when the cells were exposed to increasing lomefloxacin concentrations and a prolongation of incubation time. Moreover, it was demonstrated that the drug induced mitochondrial membrane breakdown as an early hallmark of Apoptosis. The obtained results provide a strong molecular basis for the pharmacologic effect underlying the potential use of lomefloxacin as a valuable agent for the treatment of melanoma in vivo.

Keywords

DNA fragmentation; apoptosis; lomefloxacin; melanoma; oxidative stress.

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