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Melatonin could exert antitumoral effects on hormone-dependent mammary tumors
The pineal hormone melatonin (aMT) behaves as an antiestrogenic hormone able to inhibit proliferation and invasiveness of the estrogen-dependent MCF-7 human breast cancer cells. In vivo, aMT increases the latency and reduces the incidence and growth rate of chemically induced mammary adenocarcinomas in rats. Furthermore, aMT interfere with the synthesis of steroid hormones by inhibiting the enzymes controlling the transformation from androgenic precursors, that is to say, by acting as a selective estrogen enzyme modulator (SEEM). Thus, in vitro, aMT reduces both aromatase expression and activity in MCF-7 cells. The antiaromatase activity of aMT has also been observed in vivo, and it is enough potent as to modify the growth of mammary tumors. In rats bearing estrogen-sensitive DMBA-induced mammary tumors, ovariectomy prevents the growth of these estrogen-dependent tumors. However, when these ovariectomized (ovx) animals are treated with testosterone (T), tumor growth continues because of the local aromatization of T to estrogens. This response to T is suppressed by the administration of aMT, which blocks the local synthesis of estrogens. Mammary tumors from animals treated with aMT have lower microsomal aromatase activity than tumors of control animals. Incubation of microsomal fractions of mammary tumors with aMT decreased its aromatase activity. Finally, aMT prevents the T-induced increase of uterine weight in ovx rats, which depends on the local synthesis of estrogens. All these results let us to conclude that aMT could exert antitumoral effects on hormone-dependent mammary tumors by inhibiting the aromatase activity of the tumoral tissue. This fact makes aMT an interesting compound to be tested for its possible therapeutic value in breast cancer.
Bibliographical reference:
Emilio J. Sánchez-Barceló Department of Physiology and Pharmacology, School of Medicine, University of Cantabria, Santander, Spain
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