Cytotoxicity of Manganese (III) Complex in Human Breast Adenocarcinoma Cell Line Is Mediated by the Generation of Reactive Oxygen Species Followed by Mitochondrial Damage

Abstract

Manganese (Mn) complexes are widely studied because of their important catalytic properties in synthetic and biochemical reactions. A Mn (III) complex of an amidoamine ligand was synthesized using a tetradentate amidoamine ligand. In this study, the Mn (III) complex was evaluated for its biological activity by measuring its cytotoxicity in human breast adenocarcinoma cell line (MCF-7). Cytotoxic effects of the Mn (III) complex were determined using established biomarkers in an attempt to delineate the mechanism of action and the utility of the complex as a potential anticancer drug. The Mn (III) complex induces cell death in a dose- and time-dependent manner as shown by microculture tetrazolium assay, a measure of cytotoxic cell death. Our results demonstrated that cytotoxic effects were significantly increased at higher concentrations of Mn (III) complex and with longer time of treatment. The IC (Inhibitor concentration that results in 50% cell death) value of Mn (III) complex in MCF-7 cells was determined to be 2.5 mmol/L for 24 hours of treatment. In additional experiments, we determined the Mn (III) complex-mediated cell death was due to both apoptotic and nonspecific necrotic cell death mechanisms. This was assessed by ethidium bromide/acridine orange staining and flow cytometry techniques. The Mn (III) complex produced reactive oxygen species (ROS) triggering the expression of manganese superoxide dismutase 1 and ultimately damaging the mitochondrial function as is evident by a decline in mitochondrial membrane potential. Treatment of the cells with free radical scavenger, N, N-dimethylthiourea decreased Mn (III) complex-mediated generation of ROS and attenuated apoptosis. Together, these results suggest that the Mn (III) complex-mediated MCF-7 cell death utilizes combined mechanism involving apoptosis and necrosis perhaps due to the generation of ROS.

Effect of manganese, zinc, and copper on the biological and osteogenic properties of mesoporous bioactive glass nanoparticles

“…5Mn‐MBGNs exhibited the most pronounced dose‐dependent cytotoxic effect on BMSCs with a significant increase of cell viability in the lower concentration group but a significant decrease when applied in higher concentrations. It has previously been reported that Mn shows concentration‐dependent toxic properties with pronounced systemic neurotoxicity 43‐46 . Furthermore, a very similar concentration‐dependent cytotoxic effect for 5Mn‐MBGNs has been shown before in a study conducted by our group 7 .…”

Non-immunological toxicological mechanisms of metamizole-associated neutropenia in HL60 cells

“…To chelate the added iron of hemin, we added 100 µM EDTA (29) to the reaction solution 15 minutes before addition of hemin. Further, to scavenge possible radicals 1 mM glutathione (GSH) or 1 mM N-acetylcysteine (NAC) (final concentrations) were added to the reaction solution in the same way as EDTA mentioned before.…”

Metabolic reprogramming by Dichloroacetic acid potentiates photodynamic therapy of human breast adenocarcinoma MCF-7 cells

“…After washing the cells with PBS, cells were irradiated with the laser as detailed earlier. Finally, the cells were treated with DCA for an additional 24 h. At the end of the incubation period, ROS was detected using 2’, 7’-dihydrochloroflurorescein acetate (DCFH-DA) as described earlier [ 38 ]. Briefly, DCFH-DA was added to the medium at a final concentration of 10 μM and cells were incubated for 90 min in dark.…”