Sharma Chhavi, Kaur Jatinder, Shishodia Shishir, Aggarwal Bharat B, Ralhan Ranju
Department of Biochemistry, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India.
Toxicology. 2006 Nov 10;228(1):1-15. doi: 10.1016/j.tox.2006.07.027. Epub 2006 Aug 12.
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-kappaB (NF-kappaB) 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-kappaB 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-kappaB were inhibited in curcumin pretreated oral premalignant and cancer cells in vitro. Curcumin treatment led to decreased expression of NF-kappaB 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-kappaB 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 curcumin downregulates STE (khaini) or NNK-induced NF-kappaB and COX-2 in oral premalignant and cancer cells in vitro.
在包括印度在内的东南亚地区，无烟烟草（ST）的使用是口腔癌的主要病因。最近，我们发现，在体外人体口腔细胞系统中，暴露于无烟烟草提取物（STE，嚼烟）会导致核因子-κB（NF-κB）及其下游靶点环氧合酶-2（COX-2）的表达和激活增加。本研究旨在验证姜黄素可能抑制ST暴露的口腔癌前细胞和癌细胞中NF-κB激活的假说。口腔癌前细胞和癌细胞暴露于姜黄素后，细胞活力显著降低并诱导了细胞凋亡。在体外，姜黄素预处理的口腔癌前细胞和癌细胞中，STE诱导的NF-κB核转位和DNA结合活性受到抑制。姜黄素处理导致NF-κB和COX-2的表达降低。烟草特异性亚硝胺4-（甲基亚硝胺基）-1-（3-吡啶基）-1-丁酮（NNK）是STE（嚼烟）的致癌成分之一。我们证明，姜黄素预处理可消除NNK诱导的NF-κB激活和COX-2表达，这表明NNK是姜黄素调节的STE（嚼烟）中的因素之一。总之，我们的研究结果首次证明，姜黄素在体外可下调STE（嚼烟）或NNK诱导的口腔癌前细胞和癌细胞中的NF-κB和COX-2。
