Figure 1: Melatonin antiestrogenic actions in estrogen-dependent human breast cancer cells: downregulation of the neuroendocrine/reproductive axis. Inhibition of the enzymes necessary for the conversion of adrenal androgens into estrogens in tumor surrounding tissues and in estrogen-dependent breast cancer cells. Inhibition of adenylate cyclase through binding to the MT-1 membrane receptor in epithelial malignant cells, counteracting the stimulatory effect of estradiol. Binding to the calmodulin-ERα complex, provoking destabilization of the estradiol-ERα complex, preventing its binding to DNA in both estrogen response element- (ERE-) and activator protein 1- (AP1-) containing promoters (whereas tamoxifen directly binds to the estrogen receptor, interfering with the binding of coactivators).