Melatonin and Aromatase in Breast Cancer
Samuel Cos, Carlos Martínez-Campa, Alicia V. González, Virginia Alvarez-García, Carolina Alonso-González, M. Dolores Mediavilla and Emilio J. Sánchez-Barceló
Affiliation: Departamento de Fisiología y Farmacología, Facultad de Medicina, Universidad de Cantabria, Cardenal Herrera Oria s/n, 39011 Santander, Spain.
Keywords: Aromatase, antiestrogens, breast cancer, endothelial cells, estrogens, fibroblasts, mammary tumors, MCF-7, melatonin,
pineal gland, SEEM, SERM.
It has been shown that melatonin, the pineal gland hormone, is an oncostatic agent that arrests the growth of
different kinds of tumors, especially mammary tumors whose growth is dependent of estrogens. In vivo and in vitro previous
reports point to the hypothesis that melatonin interplays with estrogen-signaling pathways at three different levels: (a)
an indirect mechanism, by interfering with the hypothalamic-pituitary-reproductive axis, in such way that the level of
plasma estrogens synthesized by the gonadal glands are down-regulated, (b) direct mechanism of the melatonin at cell
cancer level, disrupting the activation of estradiol receptors, therefore behaving as a selective estrogen receptor modulator
(SERM), and finally (c) by regulating the enzymes involved in the biosynthesis of estrogens in other tissues, thus behaving
as a selective estrogen enzyme modulator (SEEM). Melatonin has been proved to alter both the activity and expression
of several enzymes implicated in steroidal hormones synthesis, such as aromatase, the complex necessary to convert
androgens into estrogens, in different kind of cells, such as malignant epithelial cells from breast cancer and cells surrounding
the tumor: fibroblasts and endothelial cells, therefore protecting the mammary gland from estrogen induced proliferation
and transformation. The aim of the present review is to summarize the recent findings describing how melatonin
is able to modulate aromatase. Antiaromatase drugs are currently employed in breast cancer therapy and therefore melatonin
modulation of aromatase points to this indolamine as a potential anticancer drug in estrogen-dependent mammary
cancer prevention and treatment.
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