Moxifloxacin as an inducer of apoptosis in melanoma cells: A study at the cellular and molecular level

Abstract

Fluoroquinolones were shown to be cytotoxic towards various cancer cell lines, thus representing a potentially important source of new anticancer agents. The aim of the present study was to examine the effect of moxifloxacin on cell viability, redox balance and apoptosis in both amelanotic - C32 and melanotic - COLO829 melanoma cells. Herein, we found that moxifloxacin decreases the viability of C32 and COLO829 cells in concentration- and time-dependent manner. The EC₅₀ values were found to be as 0.16 mM, 0.12 mM and 0.11 mM for amelanotic C32 cells as well as 0.40 mM, 0.22 mM and 0.15 mM for COLO829 cells and 24, 48, 72 h incubation time, respectively. Moxifloxacin have also induced the intracellular disulphide imbalance and apoptosis as shown by externalization of phosphatidylserine, caspase-3/7 activation, G₂/M cell cycle arrest and DNA fragmentation. The mechanism of apoptosis was related to the loss of mitochondrial membrane potential. This is the first study that characterized cellular and molecular mechanism underlying moxifloxacin cytotoxic and pro-apoptotic effect towards melanoma cells. Although further studies are required to establish efficacy of moxifloxacin against melanoma in clinical practice, the results of current study strongly suggest, that moxifloxacin is promising candidate as a repositioned drug for anti-melanoma treatment.

Keywords: Apoptosis; DNA fragmentation; GSH depletion; Melanoma; Moxifloxacin.