期刊
CANCER RESEARCH
卷 64, 期 24, 页码 9086-9092出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-04-0313
关键词
-
类别
Tetrandrine is an antitumor alkaloid isolated from the root of Stephania tetrandra. We find that micromolar concentrations of tetrandrine irreversibly inhibit the proliferation of human colon carcinoma cells in MTT and clonogenic assays by arresting cells in G,. Tetrandrine induces G(1) arrest before the restriction point in nocodazole- and serum-starved osynchronized HT29 cells, without affecting the G(1)-S transition in aphidicolin-synchronized cells. Tetrandrine-induced G, arrest is followed by apoptosis as shown by fluorescence-activated cell sorting, terminal deoxynucleotidyl transferase-mediated nick end labeling, and annexin V staining assays. Tetrandrine-induced early G, arrest is mediated by at least three different mechanisms. First, tetrandrine inhibits purified cyclin-dependent kinase 2 (CDK2)/cyclin E and CDK4 without affecting significantly CDK2/cyclin A, CDK1/cyclin B, and CDK6. Second, tetrandrine induces the proteasome-dependent degradation of CDK4, CDK6, cyclin D1, and E2F1. Third, tetrandrine increases the expression of p53 and p21(Cip1) in wild-type p53 HCT116 cells. Collectively, these results show that tetrandrine arrests cells in G, by convergent mechanisms, including down-regulation of E2F1 and up-regulation of p53/p21(Cip1).
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据