MT-1 melatonin receptor expression increases the antiproliferative effect of melatonin on S-91 murine melanoma cells.
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 (EC50 = 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 (EC50 = 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.
Departamento de Fisiologia, Instituto de Biociências, Universidade de São Paulo, São Paulo, Brasil. kadekaal@email.uc.edu
Ana Luisa
AL
Kadekaro
Luciana N S
LN
Andrade
Lucile M
LM
Floeter-Winter
Mark D
MD
Rollag
Victoria
V
Virador
Wilfred
W
Vieira
Ana Maria de L
AM
Castrucci
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001665:Binding Sites; D002374:Catalase / Q000187:drug effects / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000187:drug effects / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008550:Melatonin / Q000494:pharmacology*; D051379:Mice; D008811:Mice, Inbred DBA; D044122:Receptor, Melatonin, MT1 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014162:Transfection; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D044122:Receptor, Melatonin, MT1; D005576:Colforsin; D000242:Cyclic AMP; D002374:Catalase; D005979:Glutathione Peroxidase; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D008550:Melatonin