Shen Guoxiang, Xu Changjiang, Hu Rong, Jain Mohit R, Gopalkrishnan Avantika, Nair Sujit, Huang Mou-Tuan, Chan Jefferson Y, Kong Ah-Ng Tony
Graduate Program in Pharmaceutical Science, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 160 Frelinghuysen Road, Piscataway, 08854, USA.
Mol Cancer Ther. 2006 Jan;5(1):39-51. doi: 10.1158/1535-7163.MCT-05-0293.
Curcumin has been shown to prevent and inhibit carcinogen-induced tumorigenesis in different organs of rodent carcinogenesis models. Our objective is to study global gene expression profiles elicited by curcumin in mouse liver and small intestine as well as to identify curcumin-regulated nuclear factor E2-related factor 2 (Nrf2)-dependent genes. Wild-type C57BL/6J and Nrf2 knockout C57BL/6J/Nrf2(-/-) mice were given a single oral dose of curcumin at 1,000 mg/kg. Liver and small intestine were collected at 3 and 12 hours after treatments. Total RNA was extracted and analyzed using Affymetrix (Santa Clara, CA) mouse genome 430 array (45K) and GeneSpring 6.1 software (Silicon Genetics, Redwood City, CA). Genes that were induced or suppressed >2-fold by curcumin treatments compared with vehicle in wild-type mice but not in knockout mice were filtered using GeneSpring software and regarded as Nrf2-dependent genes. Among those well-defined genes, 822 (664 induced and 158 suppressed) and 222 (154 induced and 68 suppressed) were curcumin-regulated Nrf2-dependent genes identified in the liver and small intestine, respectively. Based on their biological functions, these genes can be classified into the category of ubiquitination and proteolysis, electron transport, detoxification, transport, apoptosis and cell cycle control, cell adhesion, kinase and phosphatase, and transcription factor. Many phase II detoxification/antioxidant enzyme genes, which are regulated by Nrf2, are among the identified genes. The identification of curcumin-regulated Nrf2-dependent genes not only provides potential novel insights into the biological effects of curcumin on global gene expression and chemoprevention but also points to the potential role of Nrf2 in these processes.
姜黄素已被证明可预防和抑制致癌物诱导的啮齿动物致癌模型不同器官中的肿瘤发生。我们的目的是研究姜黄素在小鼠肝脏和小肠中引发的全基因组表达谱，并鉴定姜黄素调节的核因子E2相关因子2（Nrf2）依赖性基因。给野生型C57BL/6J和Nrf2基因敲除的C57BL/6J/Nrf2(-/-)小鼠单次口服剂量为1000mg/kg的姜黄素。在处理后3小时和12小时收集肝脏和小肠。提取总RNA并使用Affymetrix（加利福尼亚州圣克拉拉）小鼠基因组430阵列（45K）和GeneSpring 6.1软件（加利福尼亚州红木城的Silicon Genetics）进行分析。使用GeneSpring软件筛选与野生型小鼠中的溶剂对照相比，经姜黄素处理诱导或抑制超过2倍但在基因敲除小鼠中未出现这种情况的基因，并将其视为Nrf2依赖性基因。在这些明确的基因中，分别在肝脏和小肠中鉴定出822个（664个诱导和158个抑制）和222个（154个诱导和68个抑制）受姜黄素调节的Nrf2依赖性基因。基于它们的生物学功能，这些基因可分为泛素化和蛋白水解、电子传递、解毒、转运、凋亡和细胞周期控制、细胞粘附、激酶和磷酸酶以及转录因子等类别。许多受Nrf2调节的II期解毒/抗氧化酶基因都在已鉴定的基因之中。姜黄素调节的Nrf2依赖性基因的鉴定不仅为姜黄素对全基因组表达和化学预防的生物学效应提供了潜在的新见解，也指出了Nrf2在这些过程中的潜在作用。
