INTERACTION BETWEEN MELATONIN AND ESTRADIOL ON MORPHOLOGICAL AND MORPHOMETRIC FEATURES OF MCF-7 HUMAN BREAST-CANCER CELLS

Melatonin has been shown to have a direct inhibitory effect on the pro liferation of estrogen-responsive MCF-7 human breast cancer cells, inv olving an interaction with estradiol. The anti-proliferative effect of melatonin is reversed by the addition of estradiol to the culture. In the present study, we examined whether inhibition by melatonin and su bsequent estrogen rescue of MCF-7 cells are correlated with morphologi cal and morphometric changes in these cells. After 4 days of exposure to melatonin, MCF-7 cells showed significantly smaller cell and nuclea r sizes than other groups. These morphometric results were closely rel ated to the ultrastructural features observed in these cells. While co ntrol and estradiol-treated cells showed increased tumor characteristi cs, melatonin-treated cells presented greater differentiation, in keep ing with their epithelial origin (presence of cytokeratin filament bun dles, conspicuous rough endoplasmic reticulum, and Golgi cisternae tog ether with the presence of prominent nucleoli at the nuclear level). A dditionally, some melatonin-treated cells displayed degenerative featu res (mitochondrial swelling with disruption of cristae, cytoplasmic va cuolation, nuclear chromatin disgregation and cell lysis). The additio n of estradiol to cells previously incubated with melatonin reversed t he changes induced by the latter and these cells showed the same ultra structural features as the control cells. Our results support the noti on that melatonin exerts its antitumor effect through a cell-cycle-spe cific mechanism by delaying the entry of MCF-7 cells into mitosis. Thi s allows the tumor cells to achieve greater differentiation. The fact that the morphometric and morphological effects induced by melatonin a re counteracted by estrogens suggests a cell-cycle acceleration induce d by estradiol.