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Melatonin modulates aromatase activity in MCF‐7 human breast cancer cells
Author(s) -
Cos Samuel,
MartínezCampa Carlos,
Mediavilla Maria D.,
SánchezBarceló Emilio J.
Publication year - 2005
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1111/j.1600-079x.2004.00186.x
Subject(s) - aromatase , melatonin , medicine , mcf 7 , endocrinology , testosterone (patch) , estrogen , biology , aromatase inhibitor , cancer cell , hormone , chemistry , breast cancer , cancer , human breast
Most of the current knowledge about the mechanisms by which melatonin inhibits the growth of breast cancer cells point to an interaction of melatonin with estrogen‐responsive pathways, thus behaving as an antiestrogenic hormone. However, a possible effect of melatonin on the local synthesis of estrogens had not been examined. The objective of this work was to study whether melatonin may modify the aromatase activity in MCF‐7 breast cancer cells thus modulating the local estrogen biosynthesis. In MCF‐7 cells cultured with testosterone in estradiol‐free media, melatonin (1 n m ) counteracts the testosterone‐induced cell proliferation dependent on the local biosynthesis of estrogens from testosterone by the aromatase activity of the cells. We found that melatonin reduces the aromatase activity (measured by the tritiated water release assay) of MCF‐7 cells both at basal conditions and when aromatase activity was stimulated by cAMP or cortisol. The greatest inhibition of the aromatase activity was obtained with 1 n m melatonin, the same concentration that gives the highest antiproliferative and anti‐invasive effects of MCF‐7 cells. Finally, by RT‐PCR, we found that melatonin downregulates aromatase expression at the transcriptional level in the MCF‐7 cells. We conclude that melatonin, at physiological concentrations, decreases aromatase activity and expression in MCF‐7 cells. This aromatase inhibitory effect of melatonin, together with its already known antiestrogenic properties interacting with the estrogen‐receptor, makes this indoleamine an interesting tool to be considered in the prevention and treatment of hormone‐dependent mammary neoplasias.