Pizarro Javier G, Yeste-Velasco Marc, Esparza José Luis, Verdaguer Ester, Pallàs Mercè, Camins Antoni, Folch Jaume
Unitat de Farmacologia i Farmacognòsia, Facultat de Farmàcia, Universitat de Barcelona, Nucli Universitari de Pedralbes, Barcelona, Spain.
J Pineal Res. 2008 Aug;45(1):8-16. doi: 10.1111/j.1600-079X.2007.00548.x. Epub 2008 Feb 14.
A potential application of melatonin is its ability to rescue many cell types from cell death, because of its antioxidant properties. Likewise, recent studies suggest that melatonin may also be used as an anti-tumor drug, due to its anti-proliferative properties in tumor cells when administered at physiologic or pharmacologic doses. In the present study, we investigated the mechanisms involved in the apoptosis induced by acute exposure to melatonin and roscovitine in the rat dopaminergic neuroblastoma B65 cell line. Cell growth studies revealed that, at 24 hr of treatment, roscovitine blocked cell growth and induced apoptosis whereas melatonin delayed cell growth and induced a slight increase in the number of apoptotic nuclei. Melatonin also increased the percentage of cells in the G1-phase of the cell cycle, whereas roscovitine blocked cells in the G2/M-phase. Both compounds significantly downregulated the transcriptional activity of cdk4, while melatonin also downregulated cdk2 and cyclin D1. Taken together, our data show that melatonin at millimolar concentrations inhibits dopaminergic B65 proliferation, induces cell apoptosis, and modulates cell cycle progression by inhibiting the transcriptional activity of cyclins and cdks related to the progression of the G1-phase.
褪黑素的一个潜在应用是因其抗氧化特性而能够挽救多种细胞类型免于细胞死亡。同样，最近的研究表明，褪黑素由于在生理或药理剂量下对肿瘤细胞具有抗增殖特性，也可能被用作抗肿瘤药物。在本研究中，我们研究了大鼠多巴胺能神经母细胞瘤B65细胞系急性暴露于褪黑素和罗可辛诱导凋亡所涉及的机制。细胞生长研究表明，在处理24小时时，罗可辛阻断细胞生长并诱导凋亡，而褪黑素延迟细胞生长并导致凋亡细胞核数量略有增加。褪黑素还增加了细胞周期G1期的细胞百分比，而罗可辛使细胞停滞在G2/M期。两种化合物均显著下调cdk4的转录活性，而褪黑素还下调cdk2和细胞周期蛋白D1。综上所述，我们的数据表明，毫摩尔浓度的褪黑素抑制多巴胺能B65细胞增殖，诱导细胞凋亡，并通过抑制与G1期进展相关的细胞周期蛋白和周期蛋白依赖性激酶的转录活性来调节细胞周期进程。
