Melatonin Action on Human Breast Cancer Cells: Involvement of Glutathione Metabolism and the Redox Environment
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In spite of the evidence that melatonin inhibits breast cancer growth in vivo and in vitro (1,2), very little is known regarding the mechanism(s) of action by which this indoleamine exerts its oncostatic action (3). Recently, some progress has been made in elucidating melatonin’s mechanism of action at the cellular level using the estrogen receptor (ER) + human breast cancer cell line MCF-7. In this cell line, physiological concentrations of melatonin retard cell growth by delaying the progression of cells from G0/ G1 to S phase of the cell cycle (4). Furthermore, melatonin not only blocks estrogen-stimulated MCF-7 cell growth, but it also down-regulates the expression of ER protein as well as ER mRNA (5,6) while transiently increasing the expression of c-fos (7). Additionally, melatonin inhibits the mitogenic action of other peptide growth factors such as prolactin and epidermal growth factor (8,9). Also, the antiproliferative action of physiological levels of melatonin appears to be restricted to ER+ human breast cancer since ER- cells have little or no response to this indole (10).
KeywordsHuman Breast Cancer Cell Human Breast Cancer Cell Line Ethacrynic Acid Buthionine Sulfoximine Estrogen Receptor mRNA
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