Photosensitization by diaziquone: Correlation between diaziquone cytotoxicity and photoinduced free radicals in MCF-7 cells

Abstract

The ability of visible light to enhance the activity of diaziquone (AZQ) was evaluated in MCF-7 human breast cancer cells. Exponentially growing monolayers of MCF-7 cells were incubated for 1 hr with AZQ (IC{dollar}\sb{lcub}90{rcub}{dollar}, 0.05 {dollar}\mu{dollar}M, IC{dollar}\sb{lcub}50{rcub}{dollar}, 0.3 {dollar}\mu{dollar}M, or various concentrations of AZQ) prior to variable time intervals of visible light irradiation. Irradiations were performed using a 100W quartz-halogen lamp or 100W mercury arc lamp with a dose rate of 30 or 170 mW/m{dollar}\sp2{dollar}, respectively. The effect of visible light and/or AZQ on cellular growth was determined by clonogenic assay. The results show that MCF-7 cells were sensitive to growth inhibition by AZQ. Without AZQ, visible light irradiation had no effect on cell survival, while with AZQ, visible light potentiated its cytotoxicity by a factor of 1.6 at 10% survival. This potentiation of AZQ activity is correlated with the formation of free radicals (hydroxyl radicals and AZQ semiquinone) and with the production of DNA strand breaks as measured by electron paramagnetic resonance and gel electrophoresis, respectively. These results support the hypothesis that free radical formation is part of the mechanism of action of AZQ. Moreover, they indicate that visible light irradiation can increase the activity of AZQ and may allow its use in the treatment of tumor in human patients.