Proteomics analysis of A375 human malignant melanoma cells in response to arbutin treatment
Proteomics analysis of A375 human malignant melanoma cells in response to arbutin treatment
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DOI：
10.1016/j.bbapap.2008.09.023
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发表时间：
2009-02-01
影响因子：
3.2
通讯作者：
Cheng, Sun-Long
中科院分区：
文献类型：
--
作者：
Nawarak, Jiraporn;Huang-Liu, Rosa;Cheng, Sun-Long
虽然利用DNA微阵列技术已经阐明了熊果苷处理的A375人恶性黑色素瘤细胞的毒理学基因组学，但细胞对这种化合物的反应的蛋白质组学仍然知之甚少。在这项研究中，我们通过蛋白质组学分析来研究熊果苷对A375细胞中蛋白质表达谱的抗癌作用。以8 μ g/ml熊果苷处理A375细胞24、48和72 h后，比较对照和熊果苷处理A375细胞的蛋白质组学特征，通过MALDI-Q-TOF质谱和MS/MS鉴定26个差异表达蛋白（7个上调，19个下调）。在这些蛋白中，观察到6种相同蛋白的13种同工异构体。使用生物信息学工具搜索蛋白质功能并预测蛋白质相互作用。发现14种差异表达蛋白的相互作用网络与p53肿瘤抑制因子和细胞凋亡的下游调控有关。此外，通过RT-PCR分析，验证了3个上调蛋白（14-3-3 3g、VDAC-1和p53）和5个下调蛋白（ENPL、ENOA、IMDH2、PRDX1和VIME）在苦苷处理的A375细胞中的表达。这些蛋白质被发现在抑制癌症发展中起着重要作用。(C) 2008 Elsevier B.V.版权所有
Although the toxicogenomics of A375 human malignant melanoma cells treated with arbutin have been elucidated using DNA microarray, the proteomics of the cellular response to this compound are still poorly understood. In this study, we performed proteomic analyses to investigate the anticancer effect of arbutin on the protein expression profile in A375 cells. After treatment with arbutin (8 mu g/ml) for 24, 48 and 72 h, the proteomic profiles of control and arbutin-treated A375 cells were compared, and 26 differentially expressed proteins (7 upregulated and 19 downregulated proteins) were identified by MALDI-Q-TOF MS and MS/MS. Among these proteins, 13 isoforms of six identical proteins were observed. Bioinformatic tools were used to search for protein function and to predict protein interactions. The interaction network of 14 differentially expressed proteins was found to be correlated with the downstream regulation of p53 tumor suppressor and cell apoptosis. In addition, three upregulated proteins (14-3-3G, VDAC-1 and p53) and five downregulated proteins (ENPL, ENOA, IMDH2, PRDX1 and VIME) in arbutin-treated A375 cells were validated by RT-PCR analysis. These proteins were found to play important roles in the suppression of cancer development. (C) 2008 Elsevier B.V. All rights reserved.