Melatonin inhibits the growth of different kinds of
neoplasias, especially
breast cancer, by interacting with
estrogen-responsive pathways, thus behaving as an antiestrogenic
hormone. Recently, we described that
melatonin reduces
sulfatase expression and activity in MCF-7 human
breast cancer cells, thus modulating the local
estrogen biosynthesis. In this study, to investigate the in vivo
sulfatase-inhibitory properties of
melatonin, this indoleamine was administered to ovariectomized rats bearing DMBA-induced mammary
tumors, and treated with
estrone sulfate. In castrated animals, the growth of
estrogen-sensitive mammary
tumors depends on the local conversion of biologically inactive
estrogens to bioactive unconjugated
estrogens.
Ovariectomy significantly reduced the size and the number of the
tumors while the administration of
estrone sulfate to ovariectomized animals stimulated
tumor growth, an effect which was suppressed by
melatonin. The uterine weight of ovariectomized rats, which depends on the local synthesis of
estrogens, was increased by
estrone sulfate, except in those animals which were also treated with
melatonin. The growth-stimulatory effects of
estrone sulfate on the uterus and
tumors depend exclusively on locally formed
estrogens, since no changes in serum
estradiol were appreciated in
estrone sulfate-treated rats.
Melatonin counteracted the stimulatory effects of
estrone sulfate on
sulfatase activity and expression and incubation with
melatonin decreased the
sulfatase activity of
tumors from control animals. Animals treated with
melatonin had the same survival probability as the castrated animals and significantly higher than the uncastrated. We conclude that
melatonin could exert its antitumoral effects on
hormone-dependent mammary
tumors by down-regulating the
sulfatase pathway of the tumoral tissue.