The Major Constituent of Green Tea, Epigallocatechin-3-Gallate (EGCG), Inhibits the Growth of HPV18-Infected Keratinocytes by Stimulating Proteasomal Turnover of the E6 and E7 Oncoproteins.
The Major Constituent of Green Tea, Epigallocatechin-3-Gallate (EGCG), Inhibits the Growth of HPV18-Infected Keratinocytes by Stimulating Proteasomal Turnover of the E6 and E7 Oncoproteins.
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绿茶的主要组成部分，表藻酸酯3-甘酸酯（EGCG），通过刺激E6和E7癌蛋白的蛋白酶体周转率，抑制了HPV18感染的角质形成细胞的生长。
DOI：
10.3390/pathogens10040459
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发表时间：
2021-04-11
期刊：
影响因子：
--
通讯作者：
Dawson CW
中科院分区：
文献类型：
--
作者：
Yap JKW;Kehoe ST;Woodman CBJ;Dawson CW
表没食子儿茶素没食子酸酯(EGCG)是绿茶中主要的生物活性多酚，已被证明能抑制HPV转化的角质形成细胞的生长。在这里，我们开始研究EGCG治疗对HPV18永生化包皮角质形成细胞(HfK-HPV18)和HPV18阳性外阴上皮内瘤(VIN)克隆生长的影响，重点研究其影响细胞增殖和分化的能力，以及对病毒癌基因表达和病毒复制的影响。EGCG处理与E6和E7癌蛋白的降解及其相关的肿瘤抑制基因上调有关；因此，角质形成细胞的增殖在单层和器官型RAFT培养中都受到抑制。EGCG对细胞增殖有显著影响，但对角质形成细胞分化影响不大。在EGCG存在的情况下，晚期病毒蛋白E4的表达受到抑制，这表明EGCG能够阻止角质形成细胞分化过程中产生的病毒复制。尽管EGCG不改变E6和E7的mRNA水平，但它促进了E6和E7蛋白的周转。在EGCG处理的角质形成细胞中加入蛋白酶体抑制剂MG132可导致E6/E7蛋白的积聚，表明EGCG具有抗病毒的作用，靶向蛋白酶体介导的E6和E7蛋白的降解。
Epigallocatechin-3-gallate (EGCG), the primary bioactive polyphenol in green tea, has been shown to inhibit the growth of human papilloma virus (HPV)-transformed keratinocytes. Here, we set out to examine the consequences of EGCG treatment on the growth of HPV18-immortalised foreskin keratinocytes (HFK-HPV18) and an authentic HPV18-positive vulvar intraepithelial neoplasia (VIN) clone, focusing on its ability to influence cell proliferation and differentiation and to impact on viral oncogene expression and virus replication. EGCG treatment was associated with degradation of the E6 and E7 oncoproteins and an upregulation of their associated tumour suppressor genes; consequently, keratinocyte proliferation was inhibited in both monolayer and organotypic raft culture. While EGCG exerted a profound effect on cell proliferation, it had little impact on keratinocyte differentiation. Expression of the late viral protein E4 was suppressed in the presence of EGCG, suggesting that EGCG was able to block productive viral replication in differentiating keratinocytes. Although EGCG did not alter the levels of E6 and E7 mRNA, it enhanced the turnover of the E6 and E7 proteins. The addition of MG132, a proteasome inhibitor, to EGCG-treated keratinocytes led to the accumulation of the E6/E7 proteins, showing that EGCG acts as an anti-viral, targeting the E6 and E7 proteins for proteasome-mediated degradation.
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影响因子：
4.7
作者：
Baandrup, L.;Varbo, A.;Kjaer, S. K.
通讯作者：
Kjaer, S. K.
影响因子：
51.1
作者：
Tristram, Amanda;Hurt, Christopher N.;Griffiths, Gareth
通讯作者：
Griffiths, Gareth
影响因子：
7.2
作者：
Judson, Patricia L.;Habermann, Elizabeth B.;Virnig, Beth A.
通讯作者：
Virnig, Beth A.
DOI：
10.1124/jpet.104.076075
发表时间：
2005-03-01
影响因子：
3.5
作者：
Hsu, S;Yamamoto, T;Schuster, G
通讯作者：
Schuster, G
影响因子：
6.4
作者：
De Vuyst, Hugo;Clifford, Gary M.;Franceschi, Silvia
通讯作者：
Franceschi, Silvia