蛋白酶体
Jurkat细胞
单宁酸
细胞凋亡
细胞生长
化学
细胞周期
程序性细胞死亡
蛋白酶体抑制剂
体内
细胞生物学
生物
生物化学
T细胞
免疫学
生物技术
有机化学
免疫系统
作者
Sung-Wook Nam,Smith Dm,Dou Qp
出处
期刊:PubMed
日期:2001-10-01
卷期号:10 (10): 1083-8
被引量:38
摘要
Animal studies have demonstrated that a dietary polyphenol known as tannic acid (TA) exhibits anticarcinogenic activity in chemically induced cancers, although the involved molecular target remains unknown. In addition, proteasome inhibitors have been shown to suppress human tumor growth in nude mice. Most recently, we have reported that ester-bond-containing tea polyphenols are potent proteasome inhibitors in vitro and in vivo. We have hypothesized that TA, which contains multiple similar gallate moieties linked by ester bonds, should inhibit the proteasome activity. Here, we report that indeed TA potently and specifically inhibits the chymotrypsin-like activity of purified 20S proteasome (IC(50) = 0.06 microg/ml), 26S proteasome of Jurkat T-cell extracts, and 26S proteasome of living Jurkat cells. Inhibition of the proteasome by TA in Jurkat cells results in accumulation of two natural proteasome substrates, the cyclin-dependent kinase inhibitor p27(Kip1) and the proapoptotic protein Bax, followed by growth arrest in G1 and induction of apoptotic cell death. Our present study suggests that TA targets and inhibits the proteasome in tumor cells, which may contribute to the previously observed anticarcinogenic activity of TA.
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