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.

中文翻译：

---

MT-1褪黑素受体的表达增强了褪黑素对S-91鼠黑色素瘤细胞的抗增殖作用。

褪黑素是存在于所有脊椎动物中的一种色氨酸衍生物，最早是在牛的松果体中描述的。众所周知，褪黑激素是高度保守的分子，也存在于单细胞生物和植物中。已经描述了褪黑激素的几种作用，包括受体介导的作用和非受体介导的作用。在本文中，我们研究了褪黑激素对Cloudman S-91鼠黑色素瘤细胞体外和体内细胞增殖的影响。我们证明褪黑激素治疗可在体外显着抑制S-91黑色素瘤细胞增殖（EC50 = 10-7 m），并在体内降低肿瘤的生长。我们还证明了褪黑激素直接增加了抗氧化酶过氧化氢酶和谷胱甘肽过氧化物酶的活性。这些效应很可能是由褪黑激素的直接细胞内作用引起的，因为无法在该细胞系中证明受体的存在。通过稳定转染MT-1褪黑激素受体的表达，在S-91细胞中介导了戏剧性的抗增殖褪黑激素作用（EC50 = 10-10 m）。表达的受体通过Gi蛋白负偶联至腺苷酸环化酶/环AMP信号传导途径。这些结果表明，MT-1褪黑素受体在黑色素瘤细胞中的表达是在癌症治疗中特异性靶向细胞的潜在替代方法。