Guo Lei, Li Zhi-Song, Wang Hong-Ling, Ye Cai-Ying, Zhang De-Chang
Department of Pharmacology, School of Basic Medicine, Peking Union Medical College, Beijing 100005, China.
Eur J Pharmacol. 2006 May 24;538(1-3):15-22. doi: 10.1016/j.ejphar.2006.03.036. Epub 2006 Mar 24.
Carboxyamido-triazole (CAI), a voltage-independent calcium channel inhibitor, has been shown to be able to induce growth inhibition and apoptosis in cancer cells. In the present study, we demonstrate that CAI significantly inhibits proliferation of cultured MCF-7 human breast cancer cells in a dose-dependent manner with an IC(50) of approximately 26 microM. Reduced proliferation of MCF-7 cells in the presence of CAI correlated with accumulation of cells in G(2)/M phase and induction of apoptosis. A treatment of MCF-7 cells with 30 microM CAI caused a time-dependent decrease in the levels of proteins that regulate G(2)/M progression, including Cdk1, Cyclin B1, and Cdc25C. A simultaneous increase in the expression of p21 protein was observed. We also demonstrated a concurrent decrease of the mitochondrial membrane potential (DeltaPsi(m)), and down-regulation of anti-apoptotic protein Bcl-2. In conclusion, it seems reasonable to hypothesize that the antitumor effect of CAI in MCF-7 cells is based on G(2)/M cell cycle arrest and inducing apoptosis.
羧酰胺三唑（CAI）是一种非电压依赖性钙通道抑制剂，已被证明能够诱导癌细胞生长抑制和凋亡。在本研究中，我们证明CAI以剂量依赖性方式显著抑制培养的MCF-7人乳腺癌细胞的增殖，IC50约为26微摩尔。在CAI存在下MCF-7细胞增殖减少与细胞在G2/M期的积累和凋亡诱导相关。用30微摩尔CAI处理MCF-7细胞导致调节G2/M进程的蛋白质水平随时间下降，包括细胞周期蛋白依赖性激酶1（Cdk1）、细胞周期蛋白B1（Cyclin B1）和细胞分裂周期蛋白25C（Cdc25C）。同时观察到p21蛋白表达增加。我们还证明线粒体膜电位（ΔΨm）同时降低，抗凋亡蛋白Bcl-2下调。总之，推测CAI对MCF-7细胞的抗肿瘤作用基于G2/M期细胞周期阻滞和诱导凋亡似乎是合理的。
