The usefulness of melatonin and melatoninergic drugs in breast cancer therapy is based on its Selective Estrogen
Receptor Modulator (SERM) and Selective Estrogen Enzyme Modulator (SEEM) properties. Because of the oncostatic
properties of melatonin, its nocturnal suppression by light-at-night (LAN) has been considered a risk-factor for
breast cancer. Melatonin’s SERM actions include modulation of estrogen-regulated cell proliferation, invasiveness and
expression of proteins, growth factors and proto-oncogenes (hTERT, p53, p21, TGFβ, E-cadherin, etc.). These actions are
observable with physiologic doses of melatonin only in cells expressing ERα, and mediated by MT1 melatonin receptors.
Melatonin acts like a SEEM, inhibiting expression and activity of P450 aromatase, estrogen sulfatase and type 1, 17β-
hydroxysteroid dehydrogenase, but stimulating that of estrogen sulfotransferase. This double action mechanism (SERM
and SEEM), and the specificity for ERα bestows melatonin with potential advantages for breast cancer treatments, associated
with other antiestrogenic drugs, and idea already patented. LAN enhances the growth of rat mammary tumors by decreasing
or suppressing melatonin production. Epidemiologic studies have also described increased breast cancer risk in
women exposed to LAN. Since the strongest suppression of nocturnal melatonin occurs with wavelength light of the blue
spectral region, optical and lightening devices filtering the blue light spectrum have been proposed to avoid the risks of
light-induced suppression of nocturnal melatonin.
Keywords: Antiestrogen, aromatase, breast cancer, MCF-7, melatonin, SEEM, SERM, xenoestrogens, Melatonin, Selective Estrogen Enzyme Modulator
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