Reuter Simone, Charlet Jessica, Juncker Tom, Teiten Marie-Hélène, Dicato Mario, Diederich Marc
Laboratoire de Biologie Moléculaire et Cellulaire du Cancer, Hôpital Kirchberg, Luxembourg, Luxembourg.
Ann N Y Acad Sci. 2009 Aug;1171:436-47. doi: 10.1111/j.1749-6632.2009.04731.x.
Curcumin, a natural product isolated from the plant Curcuma longa, has a diverse range of molecular targets that influence numerous biochemical and molecular cascades. Curcumin has been shown to inhibit nuclear factor kappaB (NF-kappaB) activation at several steps in the NF-kappaB signaling pathways and thereby controls numerous NF-kappaB-regulated genes involved in various diseases. In the present study, we investigated the effect of curcumin pretreatment on 84 tumor necrosis factor-alpha (TNF-alpha)-activated genes of NF-kappaB pathways in K562 cells, using a real-time PCR array. Our results show that transcription of 29 NF-kappaB-related mRNAs was significantly downregulated (CARD4, CCL2, CD40, CSF2, F2R, ICAM1, IKBKB, IKBKE, IL1A, IL1B, IL6, IL8, IRAK2, MALT1, MAP3K1, MYD88, NFKB1, NFKB2, NFKBIA, PPM1A, RAF1, RELB, STAT1, TLR3, TNF, TNFalphaIP3, TNFSF10, and TICAM1), whereas 10 mRNAs were induced (AGT, CASP1, CSF3, FOS, IFNG, IL10, TICAM2, TLR2, TLR9, and TNFRSF7). Western blot analysis of CD40, NFKB1 (p50), RELB, NFKBIA (IkappaBalpha), and IL10 as well as an IL8 secretion assay confirmed our results. Taken together, we show that curcumin regulates an impressive number of NF-kappaB genes within the different NF-kappaB signaling pathways.
姜黄素是从植物姜黄中分离出的一种天然产物，具有多种分子靶点，可影响众多生化和分子级联反应。研究表明，姜黄素可在核因子κB（NF-κB）信号通路的多个步骤抑制NF-κB激活，从而调控众多与各种疾病相关的NF-κB调控基因。在本研究中，我们使用实时PCR阵列研究了姜黄素预处理对K562细胞中NF-κB通路84个肿瘤坏死因子-α（TNF-α）激活基因的影响。我们的结果显示，29个NF-κB相关mRNA的转录显著下调（CARD4、CCL2、CD40、CSF2、F2R、ICAM1、IKBKB、IKBKE、IL1A、IL1B、IL6、IL8、IRAK2、MALT1、MAP3K1、MYD88、NFKB1、NFKB2、NFKBIA、PPM1A、RAF1、RELB、STAT1、TLR3、TNF、TNFalphaIP3、TNFSF10和TICAM1），而10个mRNA被诱导（AGT、CASP1、CSF3、FOS、IFNG、IL10、TICAM2、TLR2、TLR9和TNFRSF7）。对CD40、NFKB1（p50）、RELB、NFKBIA（IkappaBalpha）和IL10的蛋白质免疫印迹分析以及IL8分泌测定证实了我们的结果。综上所述，我们表明姜黄素可调节不同NF-κB信号通路中数量可观的NF-κB基因。
