Green tea polyphenol epigallocatechin-3-gallate differentially modulates nuclear factor κB in cancer cells versus normal cells
Green tea polyphenol epigallocatechin-3-gallate differentially modulates nuclear factor κB in cancer cells versus normal cells
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DOI：
10.1006/abbi.2000.1742
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发表时间：
2000-04-15
影响因子：
3.9
通讯作者：
Mukhtar, H
中科院分区：
文献类型：
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作者：
Ahmad, N;Gupta, S;Mukhtar, H
在许多动物肿瘤生物测定、细胞培养系统和流行病学研究中，绿色茶表现出显着的抗炎和癌症化学预防作用。绿色茶的这些生物效应中的许多是由表没食子儿茶素3-没食子酸酯（EGCG）介导的，表没食子儿茶素3-没食子酸酯是其中存在的主要多酚。我们早先已经表明，EGCG处理导致几种癌细胞的凋亡，但不导致正常细胞的凋亡（J. Natl Cancer Inst.89，1881-1886（1997））。EGCG的这种差异反应的机制尚不清楚。在这项研究中，我们研究了在EGCG的这些差异反应中NF-κ B的参与，EGCG处理导致剂量依赖性的（i）细胞生长抑制，（ii）细胞周期的G 0/G1期停滞，和（iii）人表皮癌（A431）细胞中的凋亡诱导，但在正常人表皮角质形成细胞（NHEK）中没有，电迁移率变化分析显示，EGCG（10-80 μ M）处理导致A431细胞和NHEK中细胞质和细胞核中NF-κ B水平以剂量依赖性方式降低，尽管浓度不同。发现EGCG处理导致这些细胞中TNF-α和LPS介导的NF-κ B活化的基于剂量的差异抑制。仅在高浓度下观察到NHEK中NF-κ B组成型表达和活化的抑制。免疫印迹分析也证实了NF-κ B组成型表达的抑制以及NF-κ B/p65核蛋白的活化的类似模式。这种对TNF-α引起的NF-κ B活化的抑制是通过其抑制蛋白I κ B α的磷酸化降解介导的。总之，发现EGCG在癌细胞中与正常细胞相比赋予不同的基于剂量的NF-κ B抑制反应;即，发现在NHEK中与A431细胞相比，在高得多的EGCG剂量下发生EGCG介导的NF-κ B组成型表达和活化的抑制。本研究表明，EC; CG引起的癌细胞的细胞周期失调和细胞凋亡可通过NF-κ B抑制介导，（C）2000学术出版社。
Green tea has shown remarkable anti-inflammatory and cancer chemopreventive effects in many animal tumor bioassays, cell culture systems, and epidemiological studies. Many of these biological effects of green tea are mediated by epigallocatechin 3-gallate (EGCG), the major polyphenol present therein. We have earlier shown that EGCG treatment results in apoptosis of several cancer cells, but not of normal cells (J. Natl Cancer Inst. 89, 1881-1886 (1997)). The mechanism of this differential response of EGCG is not known. In this study, we investigated the involvement of NF-KB during these differential responses of EGCG, EGCG treatment resulted in a dose-dependent (i) inhibition of cell growth, (ii) G0/G1-phase arrest of the cell cycle, and (iii) induction of apoptosis in human epidermold carcinoma (A431) cells, but not in normal human epidermal keratinocytes (NHEK), Electromobility shift assay revealed that EGCG (10-80 mu M) treatment results in lowering of NF-KB levels in both the cytoplasm and nucleus in a dose-dependent manner in both A431 cells and NHEK, albeit at different concentrations. EGCG treatment was found to result in a dose-based differential inhibition of TNF-alpha- and LPS-mediated activation of NF-KB in these cells. The inhibition of NF-KB constitutive expression and activation in NHEK was observed only at high concentrations, The immunoblot analysis also demonstrated a similar pattern of inhibition of the constitutive expression as well as activation of NF-kappa B/p65 nuclear protein. This inhibition of TNF-alpha-caused NF-KB activation was mediated via the phosphorylative degradation of its inhibitory protein I kappa B alpha. Taken together, EGCG was found to impart differential dose-based NF-kappa B inhibitory response in cancer cells vs normal cells; i,e,, EGCG-mediated inhibition of NF-KB constitutive expression and activation was found to occur at much higher dose of EGCG in NHEK as compared to A431 cells. This study suggests that EC;CG-caused cell cycle deregulation and apoptosis of cancer cells may be mediated through NF-kappa B inhibition, (C) 2000 Academic Press.