Higashi K, Ogawara H
Department of Biochemistry, Meiji College of Pharmacy, Tokyo, Japan.
Biochim Biophys Acta. 1994 Mar 10;1221(1):29-35. doi: 10.1016/0167-4889(94)90212-7.
An isoflavone compound, daidzein, inhibits the cell proliferation of Swiss 3T3 cells. Analysis of entry in S phase of Swiss 3T3 cells reveals that daidzein blocked cell cycle G1 phase progression 4.6 h after stimulation by bombesin plus insulin. After removal of daidzein, insulin or insulin-like growth factors (IGFs) reinitiate cell cycle progression of daidzein-blocked cells without further addition of bombesin. The order in the mitogenic action of insulin or IGFs is as follows: IGF-1 (5 ng/ml) >> IGF-2 (0.5 microgram/ml) congruent to insulin (1 microgram/ml). Studies in vivo of protein kinase activation by mitogenic stimulation reveal that the treatment with daidzein decreased the activation of a MAP2 phosphorylating protein kinase (MAP2 kinase). In vitro kinase assays showed that daidzein inhibits casein kinase II activity, but does not inhibit MAP2 kinase activity. Activation of casein kinase II by polylysine augments the activity of MAP2 kinase in digitonin-permeabilized 3T3 cells. These results suggest that daidzein blocked G1 phase cell cycle progression of Swiss 3T3 by inhibiting the activity of casein kinase II which is required for the commitment of mitogenic signal by insulin or IGF-1 in G1 phase.
一种异黄酮化合物，大豆苷元，可抑制瑞士3T3细胞的细胞增殖。对瑞士3T3细胞进入S期的分析表明，在蛙皮素加胰岛素刺激4.6小时后，大豆苷元阻断了细胞周期G1期的进程。去除大豆苷元后，胰岛素或胰岛素样生长因子（IGFs）在无需进一步添加蛙皮素的情况下重新启动了被大豆苷元阻断的细胞的细胞周期进程。胰岛素或IGFs促有丝分裂作用的顺序如下：IGF-1（5纳克/毫升）>> IGF-2（0.5微克/毫升）与胰岛素（1微克/毫升）相当。对有丝分裂刺激激活蛋白激酶的体内研究表明，用大豆苷元处理可降低一种MAP2磷酸化蛋白激酶（MAP2激酶）的激活。体外激酶测定表明，大豆苷元抑制酪蛋白激酶II的活性，但不抑制MAP2激酶的活性。聚赖氨酸对酪蛋白激酶II的激活增强了洋地黄皂苷通透的3T3细胞中MAP2激酶的活性。这些结果表明，大豆苷元通过抑制酪蛋白激酶II的活性来阻断瑞士3T3细胞的G1期细胞周期进程，而酪蛋白激酶II的活性是胰岛素或IGF-1在G1期传递有丝分裂信号所必需的。
