Cytotoxicity, ROS-generation activity and radical-scavenging activity of curcumin and related compounds.
Cytotoxicity, ROS-generation activity and radical-scavenging activity of curcumin and related compounds.
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DOI：
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发表时间：
2004-03
影响因子：
2
通讯作者：
S. Fujisawa;T. Atsumi;M. Ishihara;Y. Kadoma
中科院分区：
文献类型：
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作者：
S. Fujisawa;T. Atsumi;M. Ishihara;Y. Kadoma
研究了姜黄素及其相关化合物丁香酚、丁香酚邻二聚体（bis-eugenol; 3，3 '-dimethoxy-5，5'-di-2-propylene-1，1 '-biphenyl-2，2'-diol）和异丁香酚的细胞毒性、活性氧（ROS）产生活性和自由基清除活性。它们对人下颌下腺腺癌细胞系（HSG）的细胞毒性按姜黄素>异丁香酚>双丁香酚>丁香酚的顺序下降。由于姜黄素、异丁香酚和丁香酚的疏水性（log P）为约2.5，而双丁香酚的疏水性为4.8，因此细胞毒性与log P之间没有关系。在使用5-（和-6）-羧基-2 '，7'-二氯荧光素二乙酸酯（CDFH-DA）的测定中，观察到单独的姜黄素在HSG细胞中产生细胞内ROS。姜黄素的细胞毒性和ROS生成通过添加N-乙酰基-L-半胱氨酸（NAC）和谷胱甘肽而降低，表明细胞毒性和ROS之间可能存在联系。采用近厌氧条件下过氧化苯甲酰（BPO）产生的过氧自由基引发甲基丙烯酸甲酯（MMA）聚合的诱导期法，定量测定了姜黄素及其相关化合物的自由基清除（抗氧化）活性。姜黄素的诱导（抑制）期的长度显着大于其他化合物。这表明姜黄素是过氧自由基的有效清除剂。姜黄素自由基可能与自身或与其它自由基反应以产生聚合稳定产物，如姜黄素二聚体。姜黄素的这种多酚行为与双丁香酚的多酚行为大不相同，双丁香酚像姜黄素一样具有两个羟基，或具有一个羟基的其他化合物。以2，2-二苯基-1-苦基肼（DPPH）为自由基清除剂考察了其清除自由基的活性。姜黄素清除大约一个DPPH自由基，表明姜黄素二聚体的形成。用PM 3半经验分子轨道方法研究了姜黄素二聚体的形成。基于姜黄素在低氧压下与过氧自由基的高反应性和姜黄素自由基诱导的ROS产生，提出了姜黄素预防癌症的分子机制。
The cytotoxicity, ROS (reactive oxygen species)-generation activity and radical-scavenging activity of curcumin and related compounds such as eugenol, eugenol orthodimer (bis-eugenol; 3,3'-dimethoxy-5,5'-di-2-propenyl-1,1'-biphenyl-2,2'-diol) and isoeugenol were investigated. Their cytotoxicity against a human submandibular gland adenocarcinoma cell line (HSG) declined in the order curcumin > isoeugenol > bis-eugenol > eugenol. Since the hydrophobicity (log P) of curcumin, isoeugenol and eugenol is about 2.5, whereas that of bis-eugenol is 4.8, there was no relationship between cytotoxicity and log P. Generation of intracellular ROS in HSG cells was observed for curcumin alone in an assay using 5- (and -6)-carboxy-2',7'-dichlorofluorescein diacetate (CDFH-DA). The cytotoxicity of, and ROS generation by, curcumin were reduced by the addition of N-acetyl-L-cysteine (NAC) and glutathione, suggesting a possible link between cytotoxicity and ROS. The radical-scavenging (antioxidant) activity of curcumin and related compounds was determined quantitatively by the induction period method for polymerization of methyl methacrylate (MMA) initiated by peroxy radicals derived from benzoyl peroxide (BPO) under nearly anaerobic conditions. The length of the induction (inhibition) period for curcumin was significantly greater than that of the other compounds. This suggests that curcumin is an efficient scavenger of peroxy radicals. The curcumin radical possibly reacts with itself or with other radicals to yield polymeric stable products such as curcumin dimer. Such polyphenolic behavior of curcumin was considerably different from that of bis-eugenol, which, like curcumin, has two hydroxy groups, or of other compounds with one hydroxy group. The radical-scavenging activity was also investigated with 2,2-diphenyl-1-picrylhydrazyl (DPPH). Curcumin scavenged approximately one DPPH free radical, suggesting the formation of curcumin dimer. The possible formation of curcumin dimer was explored with a PM3 semiempirical molecular orbital method. A molecular mechanism of cancer prevention by curcumin is proposed, based on its high reactivity with peroxy radicals at low oxygen pressure and on ROS generation induced by curcumin radicals.