Department of Immunology, School of Medicine, Keimyung University, Dalseo-Gu, Daegu, Korea.
J Pineal Res. 2012 Aug;53(1):99-106. doi: 10.1111/j.1600-079X.2012.00975.x. Epub 2012 Jan 31.
Melatonin (N-acetyl-5-methoxytryptamine) has differentiated the effects on apoptosis in normal and cancer cells. The mechanisms that account for the opposite effects on these cells are not adequately understood. In this study, we investigated the combined effect of melatonin and thapsigargin (TG) on apoptosis of renal cancer cells. Cotreatment with melatonin (1mm) and TG (50nm) induced approximately 10-fold expression levels of CCAAT-enhancer-binding proteins homologous protein (CHOP) compared with that of TG (50nm) alone. Downregulation of CHOP expression using small interfering RNAs markedly attenuated melatonin plus TG-mediated apoptosis. In addition, cotreatment with TG- and melatonin-induced CHOP upregulation likely relates to melatonin's antioxidant capacity because we proved that this CHOP upregulation is melatonin receptor independent. Our results collectively demonstrate that the upregulation of CHOP contributes to the enhancing effect of melatonin plus TG on apoptosis in cancer cells.
褪黑素（N-乙酰-5-甲氧基色胺）对正常细胞和癌细胞的凋亡作用有差异。导致这些细胞产生相反作用的机制尚未充分阐明。在这项研究中，我们研究了褪黑素和他普西加林（TG）联合作用对肾癌细胞凋亡的影响。与单独使用 TG（50nm）相比，褪黑素（1mm）和 TG（50nm）共同处理诱导 CCAAT 增强子结合蛋白同源蛋白（CHOP）的表达水平增加了约 10 倍。使用小干扰 RNA 下调 CHOP 的表达显著减弱了褪黑素加 TG 介导的细胞凋亡。此外，TG 和褪黑素诱导的 CHOP 上调可能与褪黑素的抗氧化能力有关，因为我们证明这种 CHOP 上调与褪黑素受体无关。我们的结果共同表明，CHOP 的上调有助于增强褪黑素加 TG 对癌细胞凋亡的作用。
