Our group focuses its research on the actions of melatonin, the main hormone produced in the pineal gland, on the genesis and development of hormone-dependent mammary tumors. In vivo, either experimental manipulations that activate the pineal gland or the exogenous administration of melatonin, reduce the incidence and development of spontaneous mammary tumors or chemically-induced mammary tumors in rodents, while pinealectomy or experimental conditions involving a reduction in melatonin synthesis stimulate mammary carcinogenesis. In vitro, melatonin inhibits proliferation and invasiveness of human breast cancer cells. The antitumoral properties of melatonin are based on its ability to interact with estrogen-signaling pathways. Two types of mechanisms have been proposed to explain these oncostatic actions of melatonin: a) downregulation of the circulating levels of gonadal estrogens, and b) direct actions at the tumoral level interfering with the activation of the estrogen receptor, therefore behaving as a SERM (selective estrogen receptor modulator). In last years, research activity in our group focuses on the description of a third mechanism by which melatonin may reduce the development of estrogen-dependent tumors, based on the ability of melatonin to modulate estrogen synthesis in both tumoral and peritumoral surrounding tissues, behaving as a SEEM (selective estrogen enzyme modulator)
The research that we are currently developing centers on:
- To study, on the one hand, the ability of melatonin to modulate the activity of some enzymes (aromatase, sulfatase, 17β-dehydrogenase, sulfotransferase) involved in the synthesis of estrogens at tumor level, and, then, to analyze the possible intracellular mediators through which melatonin regulates the activity and expression of these enzymes.
- To study the ability of melatonin to modulate the angiogenesis and to antagonize the effects of estrogens on new blood vessel formation in hormone-dependent breast cancer.
- To study the ability of melatonin to increase the sensibility of human breast cancer cells to the action of radiotherapy in base to its actions modulating the enzymes that participate in the synthesis of estrogens and its antiestrogenic actions.
- To study the protective effects of melatonin on the molecular changes induced by chemotherapy used in the treatment of breast cancer.
- To study the protective effects of chronic treatment with melatonin on cognitive and neuromorphological deficits in Ts65Dn mouse, a model of Down syndrome..