Phenolcarboxylic acids from medicinal herbs exert anticancer effects through disruption of COX-2 activity
Phenolcarboxylic acids from medicinal herbs exert anticancer effects through disruption of COX-2 activity
复制标题
草药中的酚羧酸通过破坏 COX-2 活性发挥抗癌作用
DOI：
10.1016/j.phymed.2014.05.001
复制
发表时间：
2014-09-25
期刊：
影响因子：
7.9
通讯作者：
Lu, Yin
中科院分区：
文献类型：
--
作者：
Tao, Li;Wang, Sheng;Lu, Yin
活血化瘀型中草药方剂的综合研究是中医药学最活跃的领域之一。本文致力于通过靶向肿瘤发生过程中公认的介质环氧合酶-2(COX-2)来证明这些草药中的一系列同源酚羧酸在癌症治疗中的作用。我们选择了13种典型的酚羧酸(苯甲酸衍生物、肉桂酸衍生物及其脱水缩合产物)，发现没食子酸、咖啡酸、丹参素、迷迭香酸和丹酚酸B对hCOX-2活性和A549细胞的增殖有50%的抑制作用。引入二维定量方法来描述对某些生物活性有贡献的潜在结构特征。我们还发现这些化合物与COX-2活性中心残基上的Arg120和Ser353发生了氢键作用。我们进一步广泛关注丹参素[D-(+)-β-(3，4-二羟基苯丙氨酸)]或DSS，它以COX-2依赖的方式发挥抗癌作用。基因和药物抑制COX-2均可增强DSS抑制A549细胞生长的能力。此外，COX-2/PGE(2)/ERK信号轴在DSS的抗癌作用中起重要作用。此外，DSS联合塞来昔布对A549细胞体内实验性肺转移有较强的抗癌作用。这些结果表明，酚羧酸可能通过联合靶向肿瘤细胞COX-2活性而具有抗癌作用，为临床活血化瘀型中药的肿瘤防治提供了有力证据。(C)2014年爱思唯尔股份有限公司。版权所有。
Integrated research of herbs and formulas characterized by functions of promoting blood circulation and removing blood stasis is one of the most active fields in traditional Chinese medicine. This paper strives to demonstrate the roles of a homologous series of phenolcarboxylic acids from these medicinal herbs in cancer treatment via targeting cyclooxygenase-2 (COX-2), a well-recognized mediator in tumorigenesis. We selected thirteen typical phenolcarboxylic acids (benzoic acid derivatives, cinnamic acid derivatives and their dehydration-condensation products), and found gallic acid, caffeic acid, danshensu, rosmarinic acid and salvianolic acid B showed 50% inhibitory effects on hCOX-2 activity and A549 cells proliferation. 2D-quantitative method was introduced to describe the potential structural features that contributed to certain bioactivities. We also found these compounds underwent responsible hydrogen bonding to Arg120 and Ser353 in COX-2 active site residues. We further extensively focused on danshensu [D-(+)-beta-(3,4-dihydoxy-phenylalanine)] or DSS, which exerted COX-2 dependent anticancer manner. Both genetic and pharmacological inhibition of COX-2 could enhance the ability of DSS inhibiting A549 cells growth. Additionally, COX-2/PGE(2)/ERK signaling axis was essential for the anticancer effect of DSS. Furthermore, combined treatment with DSS and celecoxib could produce stronger anticancer effects in experimental lung metastasis of A549 cells in vivo. All these findings indicated that phenolcarboxylic acids might possess anticancer effects through jointly targeting COX-2 activity in cancer cells and provided strong evidence in cancer prevention and therapy for the herbs characterized by blood-activating and stasis-resolving functions in clinic. (c) 2014 Elsevier GmbH. All rights reserved.