Cyclin D1 degradation and p21 induction contribute to growth inhibition of colorectal cancer cells induced by epigallocatechin-3-gallate.
Cyclin D1 degradation and p21 induction contribute to growth inhibition of colorectal cancer cells induced by epigallocatechin-3-gallate.
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DOI：
10.1007/s00432-012-1276-1
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发表时间：
2012-12
影响因子：
3.6
通讯作者：
Baek, Seung Joon
中科院分区：
文献类型：
--
作者：
Zhang, Xiaobo;Min, Kyung-Won;Wimalasena, Jay;Baek, Seung Joon
绿茶因其对健康的好处而受到公众的关注。表没食子儿茶素没食子酸酯(EGCG)是绿茶的主要成分，通过靶向多条信号转导通路诱导癌细胞凋亡和细胞周期停滞。不过，具体的作用机制(S)还有待确定。用四甲基偶氮唑盐比色法、细胞周期分析和caspase3/7活性检测细胞生长情况。Western blotting分析蛋白质表达。逆转录-聚合酶链式反应检测p21和细胞周期蛋白D1mRNA的表达。荧光素酶报告系统检测p21启动子活性。我们确定细胞周期蛋白D1和p21是EGCG在人结直肠癌细胞中的分子靶点。我们观察到EGCG以剂量和时间依赖的方式下调细胞周期蛋白d1，上调p21的表达。此外，我们发现EGCG降低了Cyclin D1蛋白的稳定性，从而触发了泛素依赖的蛋白酶体降解。同时，EGCG可增强p21启动子的活性，导致p21mRNA和蛋白表达上调，这可能依赖于细胞外信号调节激酶(ERK)、核因子kappaB激酶抑制因子(IKK)和磷脂酰肌醇3-激酶(PI3K)。本文提供的数据详细说明了EGCG抑制结直肠癌细胞生长的新机制。也就是说，EGCG诱导的细胞周期蛋白D1降解和p21转录激活在一定程度上导致了这些细胞的生长抑制。
The public has paid attention to green tea due to its health benefits. Epigallocatechin-3-gallate (EGCG), the major component of green tea, is well documented to induce apoptosis and cell cycle arrest in cancer cells by targeting multiple signal transduction pathways. However, the detailed mechanism(s) of action needs to be determined. Cell growth was evaluated by MTT assay, cell cycle analysis, and caspase 3/7 activity. Protein expression was analyzed through Western blotting. Reverse transcription polymerase chain reaction was used for examining mRNA expression of p21 and cyclin D1. The promoter activity of p21 was assessed by the luciferase reporter system. We identified cyclin D1 and p21 as molecular targets of EGCG in human colorectal cancer cells. We observed that cyclin D1 was down-regulated, while p21 expression was up-regulated by EGCG in dose- and time-dependent manners. Furthermore, we found EGCG decreased cyclin D1 protein stability, therefore triggering ubiquitin-dependent proteasomal degradation. Meanwhile, EGCG increased p21 promoter activity, resulting in up-regulation of p21 mRNA and protein, which was likely dependent on extracellular-signal-regulated kinase (ERK), inhibitor of nuclear factor kappa-B kinase (IKK) and phosphoinositide 3-kinase (PI3 K). The data presented here details a novel mechanism by which EGCG inhibits cell growth of colorectal cancer cells. Namely, EGCG-induced cyclin D1 degradation and p21 transcriptional activation partially contribute to growth suppression in these cells.
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影响因子：
10.5
作者：
Diehl, JA;Zindy, F;Sherr, CJ
通讯作者：
Sherr, CJ
影响因子：
64.8
作者：
Jirawatnotai S;Hu Y;Michowski W;Elias JE;Becks L;Bienvenu F;Zagozdzon A;Goswami T;Wang YE;Clark AB;Kunkel TA;van Harn T;Xia B;Correll M;Quackenbush J;Livingston DM;Gygi SP;Sicinski P
通讯作者：
Sicinski P
影响因子：
3.9
作者：
Gupta, S;Hussain, T;Mukhtar, H
通讯作者：
Mukhtar, H
DOI：
10.1006/bbrc.2000.3297
发表时间：
2000-08-28
影响因子：
3.1
作者：
Ahmad, N;Cheng, PY;Mukhtar, H
通讯作者：
Mukhtar, H
组蛋白脱乙酰基酶抑制剂trichostatin A在MCF-7乳腺癌细胞中诱导泛素依赖性细胞周期蛋白D1降解。
影响因子：
37.3
作者：
Alao, John P;Stavropoulou, Alexandra V;Lam, Eric W-F;Coombes, R Charles;Vigushin, David M
通讯作者：
Vigushin, David M