Molecular Mechanisms of Melatonin Anticancer Effects

The authors have shown that, via activation of its MT1 receptor, melatonin modulates the transcriptional activity of various nuclear receptors and the proliferation of both ER+ and ER- human breast cancer cells. Employing dominant-negative (DN) and dominant-positive (DP) G proteins, it was demonstrated that G i2 proteins mediate the suppression of estrogen-induced ER transcriptional activity by melatonin, whereas the Gq proteins mediate the enhancement of retinoid-induced RAR transcriptional activity by melatonin. In primary human breast tumors, the authors’ studies demonstrate an inverse correlation between ER and MT1 receptor expression, and confocal microscopic studies demonstrate that the MT1I receptor is localized to the caveoli and that its expression can be repressed by estrog…

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