Chen Chun-Jen, Hsu Mei-Hua, Kuo Sheng-Chu, Lai Ya-Yun, Chung Jing-Gung, Huang Li-Jiau
Graduate Institute of Pharmaceutical Chemistry, China Medical University, Taichung, ROC.
Anticancer Res. 2007 Jan-Feb;27(1A):343-9.
Ferulic acid is one of the most ubiquitous phenolic compounds in nature, which has antioxidant and anticancer activities. However, ferulic acid derivatives, such as ferulamide have never been reported.
(2E)-N,N-dibutyl-3-(4-hydroxy-3-methoxyphenyl)acrylamide (compound 8), a ferulamide derivative was synthesized in our laboratory. In this study, HL-60 cells were treated with various concentrations of compound 8, and its effects on cell growth, cell cycle, apoptosis and related measurements were investigated.
Compound 8 inhibited cell growth in a concentration- and time-dependent manner with significant cytotoxicity, and the concentration required to inhibit growth by 50% (IC50) was 8.2 microM for 24 h. The cell cycle analysis indicated that compound 8 treated cells were arrested in the G2/M-phase and followed by apoptosis. Microscopic examination showed that treatment with compound 8 displayed typical morphological features of apoptotic cells, with cell shrinking and formation of apoptotic bodies. Reverse transcription-polymerase chain reaction (RT- PCR) analysis showed a dramatic induction of CDK inhibitor p21, which inhibited the expression of cyclin B1, thereby resulting in G2/M phase arrest. After G2/M-phase arrest, cells underwent apoptosis via significant down-regulation of Bcl-2 expression.
These results enhance our understanding of the mechanisms of action of compound 8-mediated anticancer effects.
阿魏酸是自然界中最普遍存在的酚类化合物之一，具有抗氧化和抗癌活性。然而，阿魏酸衍生物，如阿魏酰胺，尚未见报道。
在我们实验室合成了一种阿魏酰胺衍生物（2E）-N，N-二丁基-3-（4-羟基-3-甲氧基苯基）丙烯酰胺（化合物8）。在本研究中，用不同浓度的化合物8处理HL-60细胞，并研究其对细胞生长、细胞周期、凋亡及相关指标的影响。
化合物8以浓度和时间依赖性方式抑制细胞生长，具有显著的细胞毒性，24小时抑制生长50%所需的浓度（IC50）为8.2微摩尔。细胞周期分析表明，经化合物8处理的细胞停滞在G2/M期，随后发生凋亡。显微镜检查显示，用化合物8处理呈现出凋亡细胞的典型形态特征，细胞皱缩并形成凋亡小体。逆转录-聚合酶链反应（RT-PCR）分析显示细胞周期蛋白依赖性激酶抑制剂p21显著诱导，其抑制细胞周期蛋白B1的表达，从而导致G2/M期停滞。在G2/M期停滞之后，细胞通过显著下调Bcl-2表达而发生凋亡。
这些结果加深了我们对化合物8介导的抗癌作用机制的理解。
