Rummel S A, Kraker A J, Steinkampf R W, Hook K E, Klohs W D
Department of Cancer Research, Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Co., Ann Arbor, MI 48105, USA.
Int J Cancer. 1995 Sep 4;62(5):636-42. doi: 10.1002/ijc.2910620524.
The mechanism of action of the novel anti-cancer compound CI-994 was studied in C26 murine colon tumor and HCT-8 human colon adenocarcinoma cells. Treatment of either cell line resulted in the specific loss of a 16-kDa phosphoprotein in a time- and concentration-dependent manner. Treatment with salicylanilide, CI-940, mimosine, aphidicolin, quercetin or ciclopirolxalamine, which, like CI-994, block cells in the G1-S phase of the cell cycle, did not affect the production of this protein. Loss of the 16-kDa protein preceded the block in cell proliferation induced by CI-994 treatment, and recovery of this protein was evident prior to the resumption of cell growth. Cellular fractionation studies demonstrated that the 16 kDa phosphoprotein is confined to the nuclear compartment. Our data indicate that loss the 16-kDa nuclear phosphoprotein appears to be a direct effect of CI-994 treatment and that the inhibition of this phosphoprotein may play a critical role in the mechanism of action of CI-994.
在C26小鼠结肠肿瘤细胞和HCT-8人结肠腺癌细胞中研究了新型抗癌化合物CI-994的作用机制。用CI-994处理这两种细胞系中的任何一种，都会导致一种16 kDa磷蛋白以时间和浓度依赖性方式特异性缺失。用水杨酰苯胺、CI-940、含羞草碱、阿非科林、槲皮素或环吡酮胺处理，这些物质与CI-994一样，会使细胞周期阻滞在G1-S期，但并不影响该蛋白的产生。CI-994处理诱导细胞增殖阻滞之前，16 kDa蛋白就已缺失，而在细胞恢复生长之前，该蛋白明显恢复。细胞分级分离研究表明，16 kDa磷蛋白局限于细胞核区室。我们的数据表明，16 kDa核磷蛋白的缺失似乎是CI-994处理的直接效应，并且该磷蛋白的抑制可能在CI-994的作用机制中起关键作用。
