Melatonin has oncostatic effects on different neoplasias, particularly on
estrogen-dependent breast cancer, by interacting with estrogen-responsive pathways,
thus behaving as an antiestrogenic hormone. In MCF-7 (a human breast
adenocarcinoma cell line), melatonin reduces both expression and activity of estrogen
sulfatase, thus modulating the local estrogen biosynthesis. In order to investigate the in
vivo sulfatase-inhibitory properties of melatonin, this indoleamine was given to
ovariectomized rats bearing DMBA-induced mammary tumors also 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
tumors while the administration of estrone sulfate to ovariectomized animals stimulated
tumor growth, an effect otherwise abrogated by melatonin. The uterine weight of
ovariectomized rats, which depends on the local synthesis of estrogens, was increased
by estrone sulfate, being this effect abolished in those animals also treated with
melatonin. The growth-stimulatory effects of estrone sulfate on the uterus and tumors
depend exclusively on locally synthesized estrogens, since no changes in serum
estradiol were observed 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 downregulating
the sulfatase pathway of the tumoral tissue.
Keywords: Breast cancer, DMBA, Melatonin, Pineal, Sulfatase.
