A liquid crystal-related compound induces cell cycle arrest at the G2/M phase and apoptosis in the A549 human non-small cell lung cancer cell line.
A liquid crystal-related compound induces cell cycle arrest at the G2/M phase and apoptosis in the A549 human non-small cell lung cancer cell line.
复制标题
液晶相关化合物可诱导 A549 人非小细胞肺癌细胞系细胞周期停滞在 G2/M 期并导致细胞凋亡。
DOI：
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发表时间：
2013
影响因子：
5.2
通讯作者：
I. Kashiwakura
中科院分区：
文献类型：
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作者：
Takuya Wakasaya;H. Yoshino;Yukako Fukushi;A. Yoshizawa;I. Kashiwakura
液晶是介于液态和晶态之间的一种物质状态，近期人们对其生物效应的兴趣日益增加。在我们近期报道的工作之后，我们研究了液晶相关化合物（LCRCs，液晶的前体）在人非小细胞肺癌A549细胞系中的细胞抑制作用。我们发现2 - (4 - 丁氧基苯基) - 5 - (4 - 羟基苯基)嘧啶（LCRC - 1）显著抑制细胞生长。用12 μM的LCRC - 1处理12小时可诱导细胞周期阻滞在G2/M期。此外，LCRC - 1增加了亚G1期细胞比例和膜联蛋白V阳性细胞数量，并激活了A549细胞中的半胱天冬酶 - 3，这表明它可以诱导这些细胞凋亡。此外，由于用泛半胱天冬酶抑制剂处理可部分抑制LCRC - 1诱导的细胞凋亡，所以看起来LCRC - 1是通过半胱天冬酶依赖性途径诱导细胞凋亡的。对LCRC - 1造成DNA损伤的能力进行了评估，但LCRC - 1没有诱导γ - H2AX（一种DNA损伤标志物）的表达。用LCRC - 1处理没有抑制WI - 38正常成纤维细胞的增殖，这使得LCRC - 1的肿瘤特异性抑制作用对于其作为一种新型抗肿瘤药物的应用具有吸引力。
Liquid crystals are the state of matter existing between liquid and crystalline phases, and recently there has been increasing interest in their biological effects. Following our recently reported work, we investigated the cell suppressive effects of liquid crystal-related compounds (LCRCs), which are precursors of liquid crystals, in the human non-small lung cancer cell line A549. We found that 2-(4-butoxyphenyl)-5-(4-hydroxyphenyl)pyrimidine (LCRC-1) dramatically suppressed cell growth. Treatment with 12 µM LCRC-1 for 12 h induced cell cycle arrest at the G2/M phase. Furthermore, LCRC-1 increased the sub-G1 fraction and Annexin V-positive cells and activated caspase-3 in A549 cells, which showed that it can induce apoptosis in these cells. Furthermore, because the induction of apoptosis by LCRC-1 was partly inhibited by treatment with pan-caspase inhibitor, it appeared that LCRC-1 induced apoptosis by a caspase-dependent pathway. The ability of LCRC-1 to cause DNA damage was assessed, but LCRC-1 did not induce expression of γ-H2AX, which is a marker of DNA damage. Treatment with LCRC-1 did not inhibit the proliferation of WI-38 normal fibroblast cells, which makes the tumor-specific suppressive effect of LCRC-1 attractive for its application as a new antitumor drug.