Differences between pulsatile or continuous exposure to melatonin on MCF-7 human breast cancer cell proliferation

We studied the different in vitro antiproliferative actions of melatonin on MCF-7 cells, depending on whether the cells are exposed to hormone concentrations which remain constant in culture media (Group I, 10(-9) M; Group II, 10(-11) M melatonin) or varying at 12 h intervals, thus simulating a diurnal rhythm: Group III, 12 h in 10(-9) M melatonin/12 h without melatonin (10(-9) M/0 12/12 h); Group IV, 10(-11) M/0 12/12 h; Group V, 10(-9) M/10(-11) M 12/12 h. After 5 days of culture, cell proliferation appeared significantly inhibited in Groups I and III, but not in Groups II and IV. However, the highest antiproliferative effect was obtained by sequential exposure to 10(-9) M/10(-11) M melatonin (Group V), which mimics the physiological rhythm of serum melatonin concentration.