Breast Cancer Therapy Based on Melatonin

摘要

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 on-costatic 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, TGFbeta, E-cadherin, etc.). These actions are observable with physiologic doses of melatonin only in cells expressing ERa, and mediated by MT_1 melatonin receptors. Melatonin acts like a SEEM, inhibiting expression and activity of P450 aromatase, estrogen sulfatase and type 1, 17beta-hydroxysteroid dehydrogenase, but stimulating that of estrogen sulfotransferase. This double action mechanism (SERM and SEEM), and the specificity for ERa 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.