Zerumbone, a tropical ginger sesquiterpene, activates phase II drug metabolizing enzymes
Zerumbone, a tropical ginger sesquiterpene, activates phase II drug metabolizing enzymes
复制标题
DOI：
10.1016/j.febslet.2004.07.042
复制
发表时间：
2004-08-13
期刊：
影响因子：
3.5
通讯作者：
Uchida, K
中科院分区：
文献类型：
--
作者：
Nakamura, Y;Yoshida, C;Uchida, K
Zerumbone（ZER）是一种存在于热带姜属植物Zerumbet Smith中的倍半萜类化合物，被认为是一种有前途的结肠癌和皮肤癌化学预防剂。在本研究中，我们研究了第二阶段解毒酶诱导ZER使用培养的大鼠正常肝上皮细胞系。RL 34细胞暴露于ZER导致谷胱甘肽S-转移酶的显著诱导，而ZER的还原类似物（α-蛇麻烯和8-羟基-α-蛇麻烯）没有显示出任何诱导作用。因此，在8位α，β-不饱和羰基处的亲电性质（其特征在于与细胞内亲核试剂（包括蛋白质巯基以及低分子量硫醇）的反应性）在II相酶的诱导中起重要作用。ZER诱导转录因子Nrf 2的核定位，Nrf 2与II相酶基因的抗氧化反应元件（ARE）结合，表明ZER是Nrf 2/ARE依赖性解毒途径的潜在激活剂。这与ZER增强几种Nrf 2/ARE依赖性II期酶基因的基因表达的观察结果一致，包括γ-谷氨酰半胱氨酸合成酶、谷胱甘肽过氧化物酶和血红素加氧酶-1。本研究还暗示了ZER激活的解毒系统在中和肝细胞脂质过氧化中的抗氧化作用，为癌症预防提供了新的见解。(C)2004年由Elsevier B. V.代表欧洲生物化学学会联合会出版。
Zerumbone (ZER), a sesquiterpene compound occurring in tropical ginger Zingiber zerumbet Smith, has been implicated as one of the promising chemopreventive agents against colon and skin cancer. In the present study, we investigated the phase II detoxification enzymes induction of ZER using a cultured rat normal liver epithelial cell line. Exposure of RL34 cells to ZER resulted in the significant induction of glutathione S-transferase, while the reduced analogues of ZER (alpha-humulene and 8-hydroxy-alpha-humulene) did not show any inducing effect. Therefore, the electrophilic property, characterized by the reactivity with intracellular nucleophiles including protein sulfhydryls as well as low molecular weight thiols, at the 8-position alpha, beta-unsaturated carbonyl group plays an important role in the induction of phase II enzymes. ZER induced nuclear localization of the transcription factor Nrf2 that binds to antioxidant response element (ARE) of the phase II enzyme genes, suggesting that ZER is a potential activator of the Nrf2/ARE-dependent detoxification pathway. This is consistent with the observation that ZER potentiated the gene expression of several Nrf2/ARE-dependent phase II enzyme genes, including gamma-glutamylcysteine synthetase, glutathione peroxidase, and hemeoxygenase-1. The present study also implied the antioxidant role of this detoxification system activation by ZER in the neutralization of lipid peroxidation in hepatocytes, providing a new insight for cancer prevention. (C) 2004 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.