Curcumin, demethtoxycurcumin, bisdemethoxycurcumin, tetrahydrocurcumin and turmerones differentially regulate anti-inflammatory and anti-proliferative responses through a ROS-independent mechanism
Curcumin, demethtoxycurcumin, bisdemethoxycurcumin, tetrahydrocurcumin and turmerones differentially regulate anti-inflammatory and anti-proliferative responses through a ROS-independent mechanism
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DOI：
10.1093/carcin/bgm123
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发表时间：
2007-08-01
期刊：
影响因子：
4.7
通讯作者：
Aggarwal, Bharat B.
中科院分区：
文献类型：
--
作者：
Sandur, Santosh K.;Pandey, Manoj K.;Aggarwal, Bharat B.
姜黄素是姜黄（Curcuma longa）的一种成分，已被证明具有化学预防活性。我们研究了姜黄素（Cur）的类似物，如去甲氧基姜黄素（DMC）、双去甲氧基姜黄素（BDMC）、四氢姜黄素（THC）和姜黄酮，是否在与姜黄素相同的程度上调节炎症信号传导和细胞增殖信号传导。结果表明，对肿瘤坏死因子（TNF）诱导的核因子 - κB（NF - κB）活化的抑制相对效力为Cur > DMC > BDMC；这表明甲氧基在苯环上的关键作用。THC在中心七碳链上缺乏共轭键，对转录因子的抑制完全没有活性。姜黄酮也未能抑制TNF诱导的NF - κB活化。NF - κB活性的抑制与NF - κB报告基因活性的抑制以及环氧合酶 - 2、细胞周期蛋白D1和血管内皮生长因子的下调相关，这些都受NF - κB调控。与NF - κB活性相反，Cur、DMC和BDMC对各种肿瘤细胞系增殖的抑制作用相当；这表明甲氧基在姜黄素的生长调节作用中作用极小。还发现THC和姜黄酮在抑制细胞生长方面也有活性，但程度远低于姜黄素、DMC和BDMC。无论是对NF - κB的抑制还是对细胞增殖的抑制，都未发现任何姜黄素类化合物与活性氧（ROS）产生有关系。总体而言，我们的结果表明，姜黄中存在的不同姜黄素类似物表现出不同的抗炎和抗增殖活性，这与其调节ROS状态的能力无关。
Curcumin, a component of turmeric (Curcuma longa), has been shown to exhibit chemopreventive activity. Whether analogs of curcumin (Cur), such as demethoxycurcumin (DMC), bisdeme-thoxycurcurnin (BDMC), tetrahydrocurcumin (THC) and turmerones, modulate inflammatory signaling and cell proliferation signaling to same extent as curcumin was investigated. The results indicate that the relative potency for suppression of tumor necrosis factor (TNF)-induced nuclear factor-kappa B (NF-kappa B) activation was Cur > DMC > BDMC; thus suggesting the critical role of methoxy groups on the phenyl ring. THC, which lacks the conjugated bonds in the central seven-carbon chain, was completely inactive for suppression of the transcription factor. Turmeronesalso failed to inhibit TNF-induced NF-kappa B activation. The suppression of NF-kappa B activity correlated with inhibition of NF-KB reporter activity and with down-regulation of cyclooxygenase-2, cyclin D1 and vascular endothelial growth factor, all regulated by NF-KB. Ita contrast to NF-KB activity, the suppression of proliferation of various tumor cell lines by Cur, DMC and BDMC was found to be comparable; indicating the methoxy groups play minimum role in the growth-modulatory effects of curcumin. THC and turmerones were also found to be active in suppression of cell growth but to a much lesser extent than curcumin, DMC and BDMC. Whether suppression of NF-KB or cell proliferation, no relationsItip of any of the curcuminoid was found with reactive oxygen species (ROS) production. Overall, our results demonstrated that different analogs of curcumin present in turmeric exhibit variable anti-inflammatory and anti-proliferative activities, which do not correlate with their ability to modulate the ROS status.