Curcumin down regulates smokeless tobacco-induced NF-κB activation and COX-2 expression in human oral premalignant and cancer cells
Curcumin down regulates smokeless tobacco-induced NF-κB activation and COX-2 expression in human oral premalignant and cancer cells
复制标题
DOI：
10.1016/j.tox.2006.07.027
复制
发表时间：
2006-11-10
期刊：
影响因子：
4.5
通讯作者：
Ralhan, Ranju
中科院分区：
文献类型：
--
作者：
Sharma, Chhavi;Kaur, Jatinder;Ralhan, Ranju
无烟烟草（ST）消费是包括印度在内的东南亚地区口腔癌的主要原因。最近，我们发现暴露于无烟烟草提取物（STE）（khaini）导致体外人口腔细胞系统中核因子-κ β（NF-κ B）及其下游靶点环氧合酶-2（考克斯-2）的表达和活化增加。本研究旨在验证姜黄素可能抑制ST暴露的口腔癌前病变和癌细胞中NF-κ B活化的假设。暴露于姜黄素的口腔癌前病变和癌细胞导致细胞活力显着下降，诱导细胞凋亡。在体外姜黄素预处理的口腔癌前病变和癌细胞中，ST诱导的核转位和NF-κ β的DNA结合活性受到抑制。姜黄素处理导致NF-κ B和考克斯-2表达降低。烟草特有的亚硝胺，4-（甲基亚硝胺基-）-1-（3-吡啶基）-1-丁酮（NNK），是STE（khaini）的致癌成分之一。我们证明姜黄素预处理消除了NNK诱导的NF-κ B和考克斯-2表达的激活，表明NNK是姜黄素调节的STE（khaini）的因素之一。总之，我们的研究结果首次证明，curcurnin下调STE（khaini）或NNK诱导的NF-κ B和考克斯-2在口腔癌前病变和癌细胞在体外。(c)2006爱思唯尔爱尔兰有限公司保留所有权利。
Smokeless tobacco (ST) consumption is a major cause of oral cancer in South East Asia including India. Recently, we showed that exposure to smokeless tobacco extract (STE) (khaini) results in increased expression and activation of nuclear factor-kappa beta (NF-kappa B) and its downstream target cyclooxygenase-2 (COX-2) in human oral cell systems in vitro. The present study was designed to test the hypothesis that curcumin may inhibit the activation of NF-kappa B in ST exposed oral premalignant and cancer cells. Exposure of oral premalignant and cancer cells to curcumin resulted in significant decrease in cell viability and induced apoptosis. STE-induced nuclear translocation and DNA-binding activity of NF-kappa beta were inhibited in curcumin pretreated oral premalignant and cancer cells in vitro. Curcumin treatment led to decreased expression of NF-KB and COX-2. The tobacco specific nitrosamine, 4-(methylnitrosamino-)-1-(3-pyridyl)-1-butanone (NNK), is one of the carcinogenic components of STE (khaini). We demonstrate that curcumin pretreatment abrogated NNK-induced activation of NF-kappa B and COX-2 expression, suggesting that NNK is one of the factors in STE (khaini) modulated by curcumin. In conclusion, our findings demonstrate for the first time that curcurnin downregulates STE (khaini) or NNK-induced NF-kappa B and COX-2 in oral premalignant and cancer cells in vitro. (c) 2006 Elsevier Ireland Ltd. All rights reserved.