Cheng Wen-Yu, Hsiang Chien-Yun, Bau Da-Tian, Chen Jaw-Chyun, Shen Wei-Shuen, Li Chia-Cheng, Lo Hsin-Yi, Wu Shih-Lu, Chiang Su-Yin, Ho Tin-Yun
Molecular Biology Laboratory, Graduate Institute of Chinese Medical Science, China Medical University, 91 Hsueh-Shih Road, Taichung 40402, Taiwan.
Pharmacol Res. 2007 Dec;56(6):474-82. doi: 10.1016/j.phrs.2007.09.009. Epub 2007 Sep 12.
Vanillin is one of the most widely used flavor compounds in food and personal products. It has been reported that vanillin is able to inhibit mutagenesis induced by chemical and physical mutagens, and to suppress the invasion and migration of cancer cells. Herein we used the oligonucleotide microarray approach to study gene expression profile of vanillin-treated human hepatocarcinoma cells. Microarray data followed by gene ontology (GO) investigation displayed that vanillin-affected clusters of genes involved in cell cycle and apoptosis. Genes down-regulated by vanillin were grouped into three GO categories, regulation of cellular process, cell cycle, and death. Furthermore, most of the down-regulated genes were associated with cancer progression. Knowledge-based analysis further indicated that Fos may play a central role in the regulation of gene expression network. Analysis of Fos-related transcription factor, activator protein 1 (AP-1), showed that vanillin inhibited AP-1 activity in a dose-dependent manner. Furthermore, the phosphorylation of extracellular signal-regulated protein kinase (ERK) was diminished with increasing concentrations of vanillin, indicating that vanillin-regulated AP-1 activity via ERK pathway. In conclusion, our data suggested that vanillin exhibited the anticancer potential by the regulations of cell cycle and apoptosis. Moreover, its regulation may involve the suppression of a central molecule, AP-1.
香草醛是食品和个人护理产品中使用最广泛的风味化合物之一。据报道,香草醛能够抑制化学和物理诱变剂诱导的诱变作用,并抑制癌细胞的侵袭和迁移。在此,我们使用寡核苷酸微阵列方法研究香草醛处理的人肝癌细胞的基因表达谱。微阵列数据随后进行基因本体论(GO)研究显示,香草醛影响参与细胞周期和凋亡的基因簇。被香草醛下调的基因被分为三个GO类别,即细胞过程调控、细胞周期和死亡。此外,大多数下调的基因与癌症进展相关。基于知识的分析进一步表明,Fos可能在基因表达网络的调控中起核心作用。对Fos相关转录因子激活蛋白1(AP-1)的分析表明,香草醛以剂量依赖的方式抑制AP-1活性。此外,随着香草醛浓度的增加,细胞外信号调节蛋白激酶(ERK)的磷酸化减少,表明香草醛通过ERK途径调节AP-1活性。总之,我们的数据表明香草醛通过调节细胞周期和凋亡表现出抗癌潜力。此外,其调节可能涉及抑制核心分子AP-1。