茶多酚（Tea Polyphenols）是茶葉中多酚類(lèi)物質(zhì)的總稱，包括黃烷醇類(lèi)、花色苷類(lèi)、黃酮類(lèi)、黃酮醇類(lèi)和酚酸類(lèi)等。其中以黃烷醇類(lèi)物質(zhì)（兒茶素）最為重要。茶多酚又稱茶鞣或茶單寧，是形成茶葉色香味的主要成份之一，也是茶葉中有保健功能的主要成份之一。
近來(lái)研究表明茶多酚能極強(qiáng)的清除有害自由基，阻斷脂質(zhì)過(guò)氧化過(guò)程，提高人體內(nèi)酶的活性，從而起到抗突變、抗癌癥的功效。據(jù)相關(guān)資料顯示，茶葉中的茶多酚(主要是兒茶素類(lèi)化合物)，對(duì)胃癌、腸癌等多種癌癥的預(yù)防和輔助治療均有益處。
茶多酚有抗擊癌細(xì)胞的強(qiáng)大生物活性。惡性腫瘤的一個(gè)主要致病因素是細(xì)胞周期動(dòng)力學(xué)的失控。近來(lái)發(fā)表在FEBS Journal雜志上的一則研究為茶多酚抗腫瘤功效又添新證據(jù)。
這項(xiàng)研究中，研究人員發(fā)現(xiàn)紅茶茶多酚、茶黃素（TF）和茶紅素（TR）能誘導(dǎo)人白血病U937和K562細(xì)胞的細(xì)胞周期阻滯在G(0) /G(1)期。研究人員的科學(xué)目標(biāo)是找出TF和TR抑制細(xì)胞周期的分子機(jī)制。科學(xué)家觀察到TF和TR夢(mèng)增強(qiáng)P19、P21和P27的表達(dá)，而CDK2、CDK4、CDK6和cyclinD1水平降低。
實(shí)驗(yàn)結(jié)果進(jìn)一步確定在阻斷細(xì)胞周期這一過(guò)程中，TF和TR抑制Akt信號(hào)發(fā)揮了重要作用。此外，抑制GSK-3β、β-catenin和FoxO1基因的表達(dá)與這些成分調(diào)控細(xì)胞周期的機(jī)制密切相關(guān)。同時(shí)TF和TR能抑制Hsp90作用在細(xì)胞周期阻滯中也起到關(guān)鍵貢獻(xiàn)作用。
更具體地說(shuō)TF和TR通過(guò)抑制Akt信號(hào)，進(jìn)而下調(diào)Wnt基因/β-catenin信號(hào)，降低cyclinD1表達(dá)，增加FoxO1基因、p27蛋白水平的表達(dá)。TF和TR抑制Hsp90的上游阻斷Akt信號(hào)，降低CDK2的表達(dá)水平。
這些結(jié)果表明TF和TR對(duì)人白血病細(xì)胞的化學(xué)預(yù)防作用機(jī)制。該研究是首次闡述多酚類(lèi)物質(zhì)這樣一個(gè)詳細(xì)的細(xì)胞周期阻斷分子機(jī)制，研究結(jié)果表明這些茶多酚物質(zhì)能顯著調(diào)控人白血病U937和K562的細(xì)胞周期，發(fā)揮抗血癌作用。（生物谷：Bioon.com）
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.
聯(lián)系客服
