Melatonin reduces the invasive capacity of MCF-7 human breast cancer cells. In vitro studies

Melatonin (MEL) has a direct oncostatic effect on estradiol (E-2) responsive MCF-7 cells in culture. The purpose of the present study was to investigate whether MEL reduces the metastatic behavior of MCF-7 cells. MEL (1 nM) reduced (p<0.001) the basal invasion of MCF-7 cells, as well as E-2-induced invasion. Sub (0.1 pM) or supra-physiological (10 mu M) concentrations of MEL lacked this effect. The pretreatment of MCF-7 cells with 1 nM MEL increased the response of tumor cells to the antiinvasive effects of this indoleamine. To explore the mechanisms involved in the antiinvasive effects of MEL, we measured its influence on these processes: a) the attachment of MCF-7 cells to a basement membrane, b) the chemotactic response of the cells, and, c) the type IV collagenolytic activity. We have concluded that: a) the presence of MEL (1 nM) in the culture media significantly reduces the ability of MCF-7 cells to attach to the basement membrane; this effect is enhanced by pretreating the cells with the same indolamine. MEL also counteracts the stimulatory effects of E-2 on cell adhesion. b) MEL (1 nM) decreases the chemotactic response of MCF-7 cells to fibronectin. c) MEL does not influence the type IV collagenolytic activity of MCF-7 cells. These results suggest that MEL not only reduces the proliferation of MCF-7 cells in vitro, but also their invasiveness, causing a decrease in cell attachment and cell motility, probably by interacting with the E-2-mediated mechanisms of MCF-7 cell invasiveness.