Melatonin: A Potential Therapeutic Option for Breast Cancer.

Melatonin has significant inhibitory effects in numerous cancers, especially breast cancer. In estrogen receptor (ER)-positive human breast cancer, the oncostatic actions of melatonin are mainly achieved by suppressing ER mRNA expression and ER transcriptional activity via the MT1 receptor. Melatonin also regulates the transactivation of nuclear receptors, estrogen-metabolizing enzymes, and the expression of related genes. Furthermore, melatonin suppresses tumor aerobic glycolysis, critical cell-signaling pathways relevant to cell proliferation, survival, metastasis, and overcomes drug resistance. Studies in animal and human models indicate that disruption of the circadian nocturnal melatonin signal promotes the growth, metabolism, and signaling of human breast cancer, resulting in resistance to hormone therapy and chemotherapy, which may be reversed by melatonin.