Nanodoses of melatonin induces apoptosis on human breast cancer cells co-cultured with colostrum cells

Abstract

The aim of this study was to investigate the effect of melatonin nanodoses adsorbed to PEG microspheres during different phases of the day on oxidative stress and apoptosis in human colostrum mononuclear (MN) cells co-cultured with breast cancer tumor cells (MCF-7). The MCF-7 cells were obtained from the American Type Culture Collection, and the MN cells were obtained from volunteer donors. The cells were preincubated for 24 h with or without 100 ng.mL-1 melatonin (MLT), PEG microspheres (PEG) or 100 ng.mL-1 MLT adsorbed to PEG microspheres (PEG-MLT). Superoxide, superoxide dismutase (SOD), intracellular calcium and apoptosis in the MN cells, MCF-7 cells and co-cultures were determined. The MN cells and co-cultured cells during the nocturnal period and the MCF-7 cells during the diurnal period exhibited increased superoxide release in the presence of PEG-MLT. MN cells treated with MLT during both periods of the day exhibited the highest SOD concentrations, whereas the MCF-7 cells had high SOD levels when incubated with PEG-MLT during the nocturnal period. The nocturnal period co-culture, independent of treatment, showed the highest levels of the enzyme. The highest amount of intracellular Ca2+ release was observed in MN cells and MCF-7 cells co-cultured with PEG-MLT during the nocturnal period. Irrespective of the phase of the day, the highest apoptosis index was observed in co-cultures of cells incubated with MLT-PEG. These data suggest that nanodoses of melatonin-modified release plus physiological melatonin produced in higher concentrations during the night can increase the effective activity of this hormone against tumors.