Melatonin decreases cell proliferation and induces melanogenesis in human melanoma SK-MEL-1 cells
Melatonin decreases cell proliferation and induces melanogenesis in human melanoma SK-MEL-1 cells
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DOI：
10.1111/j.1600-079x.2010.00765.x
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发表时间：
2010-08-01
影响因子：
10.3
通讯作者：
Quintana, Jose
中科院分区：
文献类型：
--
作者：
Cabrera, Javier;Negrin, Gledy;Quintana, Jose
褪黑素是一种在松果体中合成的吲哚胺，在释放到血液中后，它具有广泛的生物活性，包括抗肿瘤特性。在这项研究中，我们发现褪黑素降低了人类黑色素瘤细胞SK-MEL-1的生长。抗增殖作用与细胞周期阶段进展的改变以及酪氨酸酶活性的增加有关，酪氨酸酶是黑色素形成的关键调节酶。褪黑素膜受体拮抗剂（luzindole和4-P-PDOT）和一般g偶联受体抑制剂百日毒不能阻止褪黑素诱导的细胞生长停滞；这表明一个独立于g偶联膜受体的机制。相反，p38丝裂原活化蛋白激酶（p38 MAPK）信号通路似乎在褪黑激素抑制细胞生长中发挥重要作用。特异性抑制剂SB203580消除了吲哚胺诱导的p38 MAPK磷酸化和对细胞增殖的影响。此外，与n -乙酰-l-半胱氨酸和trolox等已知抗氧化剂的比较研究表明，SK-MEL-1细胞的生长对抗氧化剂高度敏感。
Melatonin is an indoleamine synthesized in the pineal gland, and after its release into the blood, it has an extensive repertoire of biological activities, including antitumoral properties. In this study, we found that melatonin reduced the growth of the human melanoma cells SK-MEL-1. The antiproliferative effect was associated with an alteration in the progression of the phases of the cell cycle and also with an increase in tyrosinase activity, the key regulatory enzyme of melanogenesis. Antagonists for melatonin membrane receptors (luzindole and 4-P-PDOT) and the general G-coupled receptor inhibitor, pertussis toxin, did not prevent the melatonin-induced cell growth arrest; this suggests a mechanism independent of G-coupled membrane receptors. In contrast, p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway seems to play a significant role in cell growth inhibition by melatonin. The indoleamine-induced phosphorylation of p38 MAPK and the effect on cell proliferation were abrogated by the specific inhibitor SB203580. Furthermore, comparative studies with known antioxidants such as N-acetyl-l-cysteine and trolox indicate that the growth of SK-MEL-1 cells is highly sensitive to antioxidants.