Melatonin and mammary cancer: a short review E J Sánchez Barceló, S Cos, R Fernández and M D Mediavilla Department of Physiology and Pharmacology, School of Medicine, University of Cantabria, 39011 Santander, Spain Abstract Melatonin is an indolic hormone produced mainly by the pineal gland. The former hypothesis of its possible role in mammary cancer development was based on the evidence that melatonin down-regulates some of the pituitary and gonadal hormones that control mammary gland development and which are also responsible for the growth of hormone-dependent mammary tumors. Furthermore, melatonin could act directly on tumoral cells, as a naturally occurring antiestrogen, thereby influencing their proliferative rate. The first reports revealed a low plasmatic melatonin concentration in women with estrogen receptor (ER) positive breast tumors. However, later studies on the possible role of melatonin on human breast cancer have been scarce and mostly of epidemiologic type. These studies described a low incidence of breast tumors in blind women as well as an inverse relationship between breast cancer incidence and the degree of visual impairment. Since light inhibits melatonin secretion, the relative increase of the melatonin circulating levels in women with a decreased light input could be interpreted as proof of the protective role of melatonin on mammary carcinogenesis. From in vivo studies on animal models of chemically-induced mammary tumorigenesis, the general conclusion is that experimental manipulations activating the pineal gland, or the administration of melatonin, lengthens the latency and reduces the incidence and growth rate of mammary tumors, while pinealectomy usually has the opposite effects. Melatonin also reduces the incidence of spontaneous mammary tumors in different kinds of transgenic mice (c-neu and N-ras) and mice from strains with a high tumoral incidence. In vitro experiments, carried out with the ER-positive MCF-7 human breast cancer cells, demonstrated that melatonin, at physiological concentration (1nM) and in presence of serum or estradiol (E): a) inhibits, in a reversible way, the cell proliferation, b) increases the expression of p53 and p21WAF1 proteins and modulates the length of the cell-cycle, c) reduces the metastasic capacity of these cells and counteracts the stimulatory effect of E on cell invasiveness; this effect is mediated, at least in part, by a melatonin-induced increase in the expression of the cell surface adhesion proteins E-cadherin and â1-integrin. The direct oncostatic effects of melatonin depends on its interaction with the tumor cell estrogen-responsive pathway. In this sense it has been demonstrated that melatonin down-regulates the expression of the ERá and inhibits the binding of the E-ER complex to the estrogen responsive element (ERE) in the DNA. The characteristics of melatonin's oncostatic actions, comprising different aspects of tumor biology as well as the physiological doses at which the effect is accomplished, give special value to these findings and encourage clinical studies on the possible therapeutic value of melatonin on breast cancer. Endocrine-Related Cancer, Vol 10, Part 2, 6/03 Remember we are NOT Doctors and have NO medical training. This site is like an Encylopedia - there are many pages, many links on many topics. Support our work with any size DONATION - see left side of any page - for how to donate. You can help raise awareness of CAM.