FEBS J：茶多酚抗肿瘤功效又添新证据

茶多酚（Tea Polyphenols）是茶叶中多酚类物质的总称，包括黄烷醇类、花色苷类、黄酮类、黄酮醇类和酚酸类等。其中以黄烷醇类物质（儿茶素）最为重要。茶多酚又称茶鞣或茶单宁，是形成茶叶色香味的主要成份之一，也是茶叶中有保健功能的主要成份之一。

近来研究表明茶多酚能极强的清除有害自由基，阻断脂质过氧化过程，提高人体内酶的活性，从而起到抗突变、抗癌症的功效。据相关资料显示，茶叶中的茶多酚(主要是儿茶素类化合物)，对胃癌、肠癌等多种癌症的预防和辅助治疗均有益处。

茶多酚有抗击癌细胞的强大生物活性。恶性肿瘤的一个主要致病因素是细胞周期动力学的失控。近来发表在FEBS Journal杂志上的一则研究为茶多酚抗肿瘤功效又添新证据。

这项研究中，研究人员发现红茶茶多酚、茶黄素（TF）和茶红素（TR）能诱导人白血病U937和K562细胞的细胞周期阻滞在G(0) /G(1)期。研究人员的科学目标是找出TF和TR抑制细胞周期的分子机制。科学家观察到TF和TR梦增强P19、P21和P27的表达，而CDK2、CDK4、CDK6和cyclinD1水平降低。

实验结果进一步确定在阻断细胞周期这一过程中，TF和TR抑制Akt信号发挥了重要作用。此外，抑制GSK-3β、β-catenin和FoxO1基因的表达与这些成分调控细胞周期的机制密切相关。同时TF和TR能抑制Hsp90作用在细胞周期阻滞中也起到关键贡献作用。

更具体地说TF和TR通过抑制Akt信号，进而下调Wnt基因/β-catenin信号，降低cyclinD1表达，增加FoxO1基因、p27蛋白水平的表达。TF和TR抑制Hsp90的上游阻断Akt信号，降低CDK2的表达水平。

这些结果表明TF和TR对人白血病细胞的化学预防作用机制。该研究是首次阐述多酚类物质这样一个详细的细胞周期阻断分子机制，研究结果表明这些茶多酚物质能显著调控人白血病U937和K562的细胞周期，发挥抗血癌作用。

doi:10.1111/j.1742-4658.2012.08668.x
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Black tea polyphenols induce human leukemic cell cycle arrest by inhibiting Akt signaling: possible involvement of Hsp90, Wnt/β-catenin signaling and FOXO1

Babli Halder, Shubho Das Gupta, Aparna Gomes^*

Tea polyphenols have potent biological activities against human cancer cells. A major causative factor of malignancies is disregulation of cell cycle kinetics. In this study we observed that black tea polyphenols, theaflavins (TF) and thearubigins (TR) induced cell cycle arrest at G₀/G₁ phase in human leukemic U937 and K562 cells. Our objective was to figure out the underlying molecular mechanism of cell cycle inhibition by TF and TR. During elucidation we observed that both TF and TR treatment augmented expression of p19, p21 and p27 while ablating CDK2, CDK4, CDK6 and cyclinD1 levels. Our experimental results further determined that Akt signaling suppression by TF and TR played a major role in this process. Moreover suppression of GSK-3β, β-catenin and amplification of FOXO1 expression was associated with regulation of certain key components of the cell cycle machinery. Additionally, depletion of Hsp90 by TF and TR also had a pivotal contribution in the cell cycle arrest. More specifically, inhibition of Akt signaling by TF and TR correlated with the depletion of its downstream targets like Wnt/β-catenin signaling, cyclinD1 and increase of FOXO1, p27 levels. Inhibition of upstream Hsp90 by TF and TR consequently attenuated Akt signaling and reduced the level of CDK2. These results suggest possible mechanisms for the chemopreventive effect of TF and TR on human leukemic cells. To our knowledge this is the first report of such a detailed molecular mechanism for TF and the less investigated polyphenol TR-mediated cell cycle inhibition in human leukemic U937 and K562 cells.