Jeong Ha-Won, Han Dong Cho, Son Kwang-Hee, Han Mi Young, Lim Jong-Seok, Ha Ji-Hong, Lee Chang Woo, Kim Hwan Mook, Kim Hyoung-Chin, Kwon Byoung-Mog
Korea Research Institute of Bioscience and Biotechnology, 52 Uendong Yoosunggu, Taejeon 305-600, South Korea.
Biochem Pharmacol. 2003 Apr 15;65(8):1343-50. doi: 10.1016/s0006-2952(03)00038-8.
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.
肉桂醛已被证明在体外对法尼基蛋白转移酶（FPTase；EC 2.5.1.29）、血管生成、细胞间黏附以及肿瘤细胞生长具有抑制作用，并且是免疫调节剂。然而，导致这些作用的机制仍不清楚。为了阐明肉桂醛衍生物CB403抑制生长的分子机制，由2'-羟基肉桂醛合成了CB403。用CB403处理的细胞与培养皿的黏附性较弱。此外，CB403以浓度依赖的方式抑制这些细胞中的肿瘤生长。使用经该化合物处理的人癌细胞进行的流式细胞术分析显示细胞周期停滞在有丝分裂期，这与细胞周期蛋白B1的量显著增加相关。此外，CB403在不使裸鼠体重减轻的情况下阻断了人结肠癌和乳腺癌异种移植瘤的体内生长。这些结果支持了肉桂醛衍生物CB403通过诱导癌细胞有丝分裂停滞发挥细胞生长抑制特性的假说。
