Antitumor effect of the cinnamaldehyde derivative CB403 through the arrest of cell cycle progression in the G2/M phase
Antitumor effect of the cinnamaldehyde derivative CB403 through the arrest of cell cycle progression in the G2/M phase
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DOI：
10.1016/s0006-2952(03)00038-8
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发表时间：
2003-04-15
影响因子：
5.8
通讯作者：
Kwon, BM
中科院分区：
文献类型：
--
作者：
Jeong, HW;Han, DC;Kwon, BM
肉桂醛已被证明对体外法尼基蛋白转移酶（FPTase; EC 2.5.1.29）、血管生成、细胞-细胞粘附和肿瘤细胞生长具有抑制作用，并且是免疫调节剂。然而，造成这些影响的机制仍然未知。为了阐明肉桂醛衍生物CB 403抑制生长的分子机制，以2 ′-羟基肉桂醛为原料合成了CB 403。CB 403处理的细胞弱粘附于培养皿。此外，CB 403以浓度依赖性方式抑制这些细胞中的肿瘤生长。使用该化合物处理的人癌细胞的FACS分析显示有丝分裂中的细胞周期停滞，这与细胞周期蛋白B1的量的显著增加相关。此外，CB 403在裸鼠中阻断人结肠和乳腺肿瘤异种移植物的体内生长，而没有体重减轻。这些结果支持了肉桂醛衍生物CB 403通过诱导癌细胞中的有丝分裂停滞而发挥细胞生长抑制特性的假设。(C)2003年爱思唯尔科学公司All rights reserved.
Cinnamaldehydes have been shown to have inhibitory effects on farnesyl protein transferase (FPTase; EC 2.5.1.29) in vitro, angiogenesis, cell-cell adhesion, and tumor cell growth and to be immunomodulators. However, the mechanisms responsible for these effects remain unknown. To elucidate the molecular mechanism of the cinnamaldehyde derivative CB403 for growth inhibition, CB403 was synthesized from 2'-hydroxycinnamaldehyde. CB403-treated cells were weakly adherent to the culture dishes. In addition, CB403 inhibited tumor growth in these cells in a concentration-dependent manner. FACS analysis using human cancer cells treated with this compound showed cell cycle arrest in mitosis, which was correlated with a marked increase in the amount of cyclin B1. Furthermore, CB403 blocked in vivo growth of human colon and breast tumor xenografts without loss of body weight in nude mice. These results support the hypothesis that the cinnamaldehyde derivative CB403 exerts cytostatic properties by inducing mitotic arrest in cancer cells. (C) 2003 Elsevier Science Inc. All rights reserved.