Toxicogenomics of kojic acid on gene expression profiling of A375 human malignant melanoma cells
Toxicogenomics of kojic acid on gene expression profiling of A375 human malignant melanoma cells
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DOI：
10.1248/bpb.29.655
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发表时间：
2006-04-01
影响因子：
2
通讯作者：
Tsay, GJ
中科院分区：
文献类型：
--
作者：
Cheng, SL;Liu, RH;Tsay, GJ
曲酸是一种天然产物，通常用作食品添加剂和防腐剂、化妆品中的皮肤增白剂、植物生长调节剂和化学中间体。采用DNA微阵列技术，研究了曲酸对人皮肤A375恶性黑色素瘤细胞基因表达谱的整体生物学效应。经曲酸处理后，共有361个差异表达基因发生显著变化，其中上调基因136个，下调基因225个。我们利用生物信息学工具搜索差异表达基因的基因本体和类别分类，为表达基因在黑色素形成调控中的细胞成分、分子功能和生物过程提供有用的信息。APOBEC1、ARBGEF16、CD22、FGFR3、GALNT1、UNC5C和ZNF146等7个下调基因经实时定量PCR （RT-qPCR）分析技术典型验证为黑色素瘤癌细胞中的抑瘤基因。因此，微阵列技术与RT-qPCR相结合，为探索曲酸应答的差异表达基因数量及其生物学功能提供了高通量的方法，使人们对曲酸对皮肤癌治疗的作用及相关副作用有了更多的了解。此外，差异表达基因可能成为皮肤恶性黑色素瘤进一步诊断和治疗应用的有用标记。
Kojic acid is a natural product and normally used as a food additive and preservative, a skin-whitening agent in cosmetics, a plant growth regulator and a chemical intermediate. Using DNA microarray technology, the overall biological effects of kojic acid on the gene expression profiling of a human skin A375 malignant melanoma cells were examined. After treatment with kojic acid, a total of 361 differentially expressed genes were distinctively changed with 136 up-regulated genes and 225 down-regulated genes. We used the bioinformatics tool to search the gene ontology and category classification of differentially expressed genes that provided the useful information of expressed genes belonging to cellular component, molecular function and biological process in regulation of melanogenesis. Seven down-regulated genes of APOBEC1, ARBGEF16, CD22, FGFR3, GALNT1, UNC5C and ZNF146 that were typically validated by the real-time quantitative PCR (RT-qPCR) analysis technology showed to be the tumor suppressor genes in melanoma cancer cells. Thus, microarray technology coupled with RT-qPCR offered a high throughput method to explore the number of differentially expressed genes responding to kojic acid and their biological functions, and led to more understanding of kojic acid effects on skin cancer therapy and related side effects. Moreover, the differentially expressed genes may become useful markers of skin malignant melanoma for further diagnostic and therapeutic applications.