Liquid crystal-related compound-induced cell growth suppression and apoptosis in the chronic myelogenous leukemia K562 cell line
Liquid crystal-related compound-induced cell growth suppression and apoptosis in the chronic myelogenous leukemia K562 cell line
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DOI：
10.1007/s10637-010-9430-6
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发表时间：
2011-10
影响因子：
3.4
通讯作者：
Yukako Fukushi;M. Hazawa;Kenji Takahashi;A. Yoshizawa;I. Kashiwakura
中科院分区：
文献类型：
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作者：
Yukako Fukushi;M. Hazawa;Kenji Takahashi;A. Yoshizawa;I. Kashiwakura
液晶是一种介于液体和晶体之间的物质状态，近年来人们对其生物效应产生了浓厚的兴趣。我们之前的研究表明，液晶相关化合物（liquid crystal related compounds, LCRCs）是液晶的前体，在相对较低的浓度下可以促进造血分化（Biol Pharm Bull, 32, 2009）。然而，lcrc对肿瘤细胞的生物学潜力尚不清楚。本研究评估了16种lcrc对慢性髓性白血病细胞系K562的生物学活性。结果表明，2-（4-丁氧基苯基）-5-（4-羟基苯基）嘧啶（化合物7）和2-{4-（4-己氧基苯基）苯基}-5-羟基嘧啶（化合物9）在μM范围内对K562细胞的生长有明显的抑制作用。这些化合物在结构上相似，核心是三个芳香环，包括一个嘧啶环和一个烷基链和一个氢氧根在两边的残基。此外，只有化合物7能诱导p38丝裂原活化蛋白激酶和c-Jun n-末端激酶的活化，导致K562细胞凋亡。化合物7和9的对比结果表明，两种化合物抑制细胞增殖的机制不同。这些结果提示lcrc作为新型抗肿瘤药物应用的可能性。
Liquid crystals are the state of matter existing between the liquid and the crystalline phase, and there is a recent surging interest in its biological effects. Our previous study showed that liquid crystal-related compounds (LCRCs), which are precursors of the liquid crystal, enhanced hematopoietic differentiation at a relatively low concentration (Biol Pharm Bull, 32, 2009). However, biological potentials of LCRCs on tumor cells are unclear. In this study, the biological activity of 16 LCRCs to a chronic myelogenous leukemia cell line, K562, was evaluated. As a result, two compounds, 2-(4-butoxyphenyl)-5-(4-hydroxyphenyl)pyrimidine (compound 7) and 2-{4-(4-hexyloxyphenyl)phenyl}-5-hydroxypyrimidine (compound 9) showed marked growth suppression of K562 cells at μM range. These compounds are similar in structure with a core of three aromatic rings including a pyrimidine ring and residues of one alkyl chain and one hydroxide on either side. In addition, only compound 7 induced the activation of p38 mitogen-activated protein kinase and c-Jun N-terminal kinase, and apoptosis of K562 cells. The contrasting results between compounds 7 and 9 indicate different mechanisms to suppress the cell proliferation between the two compounds. These results suggest the possibility of LCRCs for application as new antitumor drugs.