Suppressive effects of liquid crystal compounds on the growth of the A549 human lung cancer cell line
Suppressive effects of liquid crystal compounds on the growth of the A549 human lung cancer cell line
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DOI：
10.1007/s10637-010-9411-9
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发表时间：
2011-08-01
影响因子：
3.4
通讯作者：
Kashiwakura, Ikuo
中科院分区：
文献类型：
--
作者：
Takahashi, Yuuka;Hazawa, Masaharu;Kashiwakura, Ikuo
本研究的目的是评价几种两亲性液晶化合物（含d-氨基葡萄糖胺的苯基嘧啶衍生物和含末端羟基的氰联苯衍生物）的生物活性和药理活性，以探索其新的抗癌功能。通过流式细胞仪和Western blot分析，对LCs在A549人肺癌细胞中的生长、细胞周期分布和细胞信号通路进行了研究。此外，我们还观察了lc对WI-38正常成纤维细胞生长的影响。因此，苯基嘧啶衍生物和氰联苯衍生物在A549细胞中表现出细胞抑制作用，通过G1期阻滞抑制细胞生长。进一步的分析使用苯基嘧啶衍生物和前体的氰联苯化合物证明了结构-活性关系。其中一种苯基嘧啶衍生物抑制A549的生长，对正常成纤维细胞无任何毒性。因此，一种新的药理功能被假设为LCs本身结构中固有的，因此，肿瘤特异性活性依赖于苯基嘧啶衍生物的疏水性基团仍然是一个有趣的问题。我们的研究结果表明，LCs本身可能作为一种新型的化疗药物。
The aim of this study was to evaluate the biological activity and pharmacological activity of several amphiphilic liquid-crystalline compounds (LCs), i.e. phenylpyrimidine derivatives possessing D-glucamine and cyanobiphenyl derivatives with a terminal hydroxyl unit, to explore novel anti-cancer functions of the LCs. The anti-cancer properties of the LCs were investigated in A549 human lung cancer cells by assessing cell growth, cell cycle distribution, and cell signaling pathways using a flow cytometer and a Western blot analysis. In addition, the effect of LCs on the growth of WI-38 normal fibroblasts was examined. Consequently, the phenylpyrimidine derivatives and cyanobiphenyl derivatives showed cytostatic effects, causing the suppression of cell growth through G1 phase arrest in A549 cells. Further analyses using phenylpyrimidine derivatives and precursors of a cyanobiphenyl compound demonstrated the structure-activity relationships. One of the phenylpyrimidine derivatives inhibited A549 growth without any toxicity to normal fibroblasts. As a result, a novel pharmacological function was hypothesized to be inherent in the structure of the LCs themselves, and the dependence of the tumor-specific activity on the hydrophobic group of phenylpyrimidine derivatives therefore remains an interesting issue. Our results suggest the possibility that the LCs themselves may act as a novel type of chemotherapeutic agent.