Unique proteomic features induced by a potential antiglioma agent, Nordy (dl-nordihydroguaiaretic acid), in glioma cells
Unique proteomic features induced by a potential antiglioma agent, Nordy (dl-nordihydroguaiaretic acid), in glioma cells
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潜在的抗神经胶质瘤药物 Nordy（dl-去甲二氢愈创木酸）在神经胶质瘤细胞中诱导独特的蛋白质组特征
DOI：
10.1002/pmic.200700054
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发表时间：
2008-02-01
期刊：
影响因子：
3.4
通讯作者：
Wang, Ji Ming
中科院分区：
文献类型：
--
作者：
Bian, Xiu-Wu;Xu, Jian-Ping;Wang, Ji Ming
Nordy是天然脂氧合酶抑制剂去甲二氢愈创木酸的手性合成化合物。在本研究中，我们发现诺帝在体外抑制人脑胶质瘤细胞系的生长及其在小鼠体内的致瘤性。此外，Nordy促进高度恶性的人类神经胶质瘤细胞的分化。对Nordy活性的机制基础的研究表明，它改变了肿瘤细胞中蛋白质表达谱的模式。通过双向电泳，我们发现在人脑胶质瘤细胞系中，至少有六个蛋白在Nordy处理后下调，而在同一细胞中有四个蛋白升高。在6个下调的蛋白质中，MALDI TOF MS微测序证实了5个蛋白质的身份：增殖相关基因A（PAG-A），选择性剪接因子-3（ASF-3），β-半乳糖苷结合凝集素，真核翻译起始因子5A（eIF-5A）和coffilin-1（非肌肉）。四种上调的蛋白质是GST-π、甘油醛-3-磷酸脱氢酶、α-烯醇化酶和亲环素。所有这些蛋白质都被报道参与关键的细胞功能，包括增殖、代谢、分化、凋亡和基因转录。我们的研究结果表明，Nordy可能是一种有前途的药物，用于开发新型抗肿瘤药物，靶向在多个水平上控制肿瘤细胞功能的蛋白质。
Nordy is a chirally synthesized compound of a natural lipoxygenase inhibitor nordihydroguaiaretic acid. In this study, we found that Nordy inhibited the growth of human glioma cell lines in vitro and their tumorigenicity in mice. In addition, Nordy promoted differentiation of highly malignant human glioma cells. Investigation into the mechanistic basis of Nordy activities revealed that it altered the pattern of protein expression profiles in tumor cells. By using 2-DE, we found that in human glioma cell lines, at least six proteins were down-regulated after Nordy treatment, while four proteins were elevated in the same cells. Among the six down-regulated proteins, microsequencing with MALDI TOF MS confirmed the identity of five: proliferation-associated gene A (PAG-A), alternative splicing factor-3 (ASF-3), P-galactoside binding lectin, eukaryotic translation initiation factor 5A (eIF-5A), and coffilin-1 (nonmuscle). Four upregulated proteins were GST-pi, glyceraldehyde-3-phosphate dehydrogenase, alpha-enolase, and cyclophilin. All these proteins have been reported to participate in key cellular functions including proliferation, metabolism, differentiation, apoptosis, and gene transcription. Our results suggest that Nordy may constitute a promising drug lead for the development of novel antitumor agents targeting proteins that control tumor cell function at multiple levels.