Time- and dose-dependent effects of curcumin on gene expression in human colon cancer cells.
Time- and dose-dependent effects of curcumin on gene expression in human colon cancer cells.
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DOI：
10.1186/1477-3163-3-8
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发表时间：
2004-05-12
影响因子：
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通讯作者：
Van Ommen B
中科院分区：
文献类型：
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作者：
Van Erk MJ;Teuling E;Staal YC;Huybers S;Van Bladeren PJ;Aarts JM;Van Ommen B
姜黄素是一种香料和着色食品化合物，在预防结肠癌方面具有广阔的前景。姜黄素可防止接受结肠致癌剂治疗的大鼠结肠肿瘤的发展，在结肠癌细胞中，姜黄素可以抑制细胞增殖并诱导细胞凋亡，它是一种抗氧化剂，并且可以充当抗炎剂。本研究的目的是利用基因表达谱阐明姜黄素在结肠癌细胞中的机制和作用。使用具有 4000 个人类基因的 cDNA 微阵列，在两种人类结肠癌细胞系中研究了姜黄素暴露引起的基因表达变化。将 HT29 细胞暴露于两种不同浓度的姜黄素，并及时跟踪基因表达变化（3、6、12、24 和 48 小时）。还在第二种细胞类型 Caco-2 细胞中研究了短期（3 或 6 小时）姜黄素暴露后基因表达的变化。在所有时间点均发现基因表达变化（>1.5 倍）。 HT29 细胞比 Caco-2 细胞对姜黄素更敏感。早期反应基因涉及细胞周期、信号转导、DNA修复、基因转录、细胞粘附和外源代谢。在 HT29 细胞中，姜黄素调节许多细胞周期基因，其中一些基因在 G2/M 期的过渡中发挥作用。这对应于流式细胞术观察到的细胞周期停滞在 G2/M 期。具有相似表达谱的功能组包括参与姜黄素 12 和 24 小时后诱导的 II 期代谢的基因。在 HT29 和 Caco-2 细胞中，姜黄素下调了一些细胞色素 P450 基因的表达。此外，姜黄素还影响金属硫蛋白基因、微管蛋白基因、p53和其他与结肠癌发生有关的基因的表达。这项研究扩展了有关已报道受姜黄素影响的途径或过程的知识（细胞周期停滞，II 期基因）。此外，还发现了姜黄素在预防结肠癌中发挥作用的基因和途径的潜在新线索。
Curcumin is a spice and a coloring food compound with a promising role in colon cancer prevention. Curcumin protects against development of colon tumors in rats treated with a colon carcinogen, in colon cancer cells curcumin can inhibit cell proliferation and induce apoptosis, it is an anti-oxidant and it can act as an anti-inflammatory agent. The aim of this study was to elucidate mechanisms and effect of curcumin in colon cancer cells using gene expression profiling. Gene expression changes in response to curcumin exposure were studied in two human colon cancer cell lines, using cDNA microarrays with four thousand human genes. HT29 cells were exposed to two different concentrations of curcumin and gene expression changes were followed in time (3, 6, 12, 24 and 48 hours). Gene expression changes after short-term exposure (3 or 6 hours) to curcumin were also studied in a second cell type, Caco-2 cells. Gene expression changes (>1.5-fold) were found at all time points. HT29 cells were more sensitive to curcumin than Caco-2 cells. Early response genes were involved in cell cycle, signal transduction, DNA repair, gene transcription, cell adhesion and xenobiotic metabolism. In HT29 cells curcumin modulated a number of cell cycle genes of which several have a role in transition through the G2/M phase. This corresponded to a cell cycle arrest in the G2/M phase as was observed by flow cytometry. Functional groups with a similar expression profile included genes involved in phase-II metabolism that were induced by curcumin after 12 and 24 hours. Expression of some cytochrome P450 genes was downregulated by curcumin in HT29 and Caco-2 cells. In addition, curcumin affected expression of metallothionein genes, tubulin genes, p53 and other genes involved in colon carcinogenesis. This study has extended knowledge on pathways or processes already reported to be affected by curcumin (cell cycle arrest, phase-II genes). Moreover, potential new leads to genes and pathways that could play a role in colon cancer prevention by curcumin were identified.