Lomefloxacin Induces Oxidative Stress and Apoptosis in COLO829 Melanoma Cells

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2017

Erschienen:

2017

Enthalten in:

Zur Gesamtaufnahme - volume:18

Enthalten in:

International journal of molecular sciences - 18(2017), 10 vom: 20. Okt.

Sprache:

Englisch

Beteiligte Personen:

Beberok, Artur [VerfasserIn]
Wrześniok, Dorota [VerfasserIn]
Szlachta, Martyna [VerfasserIn]
Rok, Jakub [VerfasserIn]
Rzepka, Zuzanna [VerfasserIn]
Respondek, Michalina [VerfasserIn]
Buszman, Ewa [VerfasserIn]

Links:

Volltext

Themen:

Apoptosis
DNA fragmentation
Fluoroquinolones
Journal Article
L6BR2WJD8V
Lomefloxacin
Melanoma
Oxidative stress
Reactive Oxygen Species

Anmerkungen:

Date Completed 06.06.2018

Date Revised 13.11.2018

published: Electronic

Citation Status MEDLINE

doi:

10.3390/ijms18102194

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM277219841