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MT‐1 melatonin receptor expression increases the antiproliferative effect of melatonin on S‐91 murine melanoma cells
Author(s) -
Kadekaro Ana Luisa,
Andrade Lucia. S.,
FloeterWinter Lucile M.,
Rollag Mark D.,
Virador Victoria,
Vieira Wilfred,
Castrucci Ana Maria de L.
Publication year - 2004
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.2004.00119.x
Subject(s) - melatonin , melatonin receptor , receptor , biology , medicine , endocrinology , cell culture , in vivo , pinealocyte , adenylyl cyclase , cell growth , luzindole , pineal gland , pars tuberalis , intracellular , microbiology and biotechnology , biochemistry , pituitary gland , genetics , hormone
Melatonin, a derivative of tryptophan that is present in all vertebrates, was first described in bovine pineal gland. It is known that melatonin is a highly conserved molecule, present also in unicellular organisms and plants. Several effects of melatonin have been described, including receptor‐ and non‐receptor‐mediated actions. Herein, we studied the effects of melatonin on in vitro and in vivo cell proliferation of Cloudman S‐91 murine melanoma cells. We demonstrated that melatonin treatment significantly inhibits S‐91 melanoma cell proliferation in vitro (EC 50 = 10 −7 m ) as well as reduces tumor growth in vivo. We also demonstrated that melatonin directly increases the activity of the antioxidant enzymes catalase and glutathione peroxidase. These effects are most likely triggered through the direct intracellular action of melatonin, since the presence of receptors could not be demonstrated in this cell line. Expression of MT‐1 melatonin receptor by stable transfection, mediated a dramatic antiproliferative melatonin effect (EC 50 = 10 −10 m ) in S‐91 cells. The expressed receptor is negatively coupled to the adenylyl cyclase/cyclic AMP signaling pathway via Gi protein. These results suggest that expression of the MT‐1 melatonin receptor in melanoma cells is a potential alternative approach to specifically target cells in cancer therapeutic treatment.