MT-1 melatonin receptor expression increases the antiproliferative effect of melatonin on S-91 murine melanoma cells

被引:58
作者
Kadekaro, AL
Andrade, LNS
Floeter-Winter, LM
Rollag, MD
Virador, V
Vieira, W
Castrucci, AMD
机构
[1] Univ Sao Paulo, Inst Biociencias, Dept Fisiol, Sao Paulo, Brazil
[2] Univ Sao Paulo, Inst Ciencias Biomed, Dept Parasitol, Sao Paulo, Brazil
[3] Uniformed Serv Univ Hlth Sci, Dept Anat & Cell Biol, Bethesda, MD 20814 USA
[4] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA
关键词
melatonin; melatonin receptors; murine melanoma; S-91 cell line; tumor growth;
D O I
10.1111/j.1600-079X.2004.00119.x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:204 / 211
页数:8
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