Aim: 

Melatonin exerts oncostatic effects on different kinds of neoplasias, especially on estrogen-dependent mammary tumors. The intratumoral production of estrogens in breast carcinoma tissue plays a pivotal role in the proliferation of mammary tumoral cells and its blockade is one of the main objectives of the treatment of breast cancer. The aim of the present work is centered on the study of the role of melatonin in the control of some enzymes involved in the formation and transformation of estrogens in human breast cancer cells.

Methods: 

Expression of the mRNA from different enzymes was carried out by real time polymerase chain reaction (QPCR) in MCF-7 cells. The different activities were measured by transformation of the adequate tritiated substrates into the correspondent estrogens.

Results: 

The present study demonstrates that melatonin, at physiological concentrations, modulates the synthesis and transformation of biologically active estrogens in MCF-7 cells, through the inhibition of aromatase, sulfatase and 17b-hydroxysteroid dehydrogenase type 1 activity and expression, enzymes involved in the estradiol formation in breast cancer cells. Physiological concentrations of melatonin also stimulate the activity and expression of estrogen sulfotransferase, the enzyme responsible for the formation of the biologically inactive estrogen sulfates.

Conclusion: 

Since the inhibition of enzymes involved in the biosynthesis of estrogens is currently one of the first therapeutic strategies used against the growth of breast cancer, melatonin modulation of different enzymes involved in the synthesis of steroid hormones makes, collectively, this indolamine an interesting anticancer drug in the prevention and treatment of estrogen-dependent mammary tumors.

Supported by the Spanish MCYT (SAF2007-60659 and 62762)