Quercetin increased bioavailability and decreased methylation of green tea polyphenols in vitro and in vivo.
Quercetin increased bioavailability and decreased methylation of green tea polyphenols in vitro and in vivo.
复制标题
DOI：
10.1039/c2fo10254d
复制
发表时间：
2012-06
期刊：
影响因子：
6.1
通讯作者：
Henning SM
中科院分区：
文献类型：
--
作者：
Wang P;Heber D;Henning SM
绿色茶多酚（GTP）在体内的广泛甲基化可能限制其化学预防潜力。我们研究了是否槲皮素，儿茶酚-O-甲基转移酶（COMT）和多药耐药蛋白（MRPs）的天然抑制剂，将差异增加细胞内浓度和降低不同癌细胞系中GTP的甲基化。内源性COMT活性在肺癌A549细胞中最低，在肾786-O细胞中居中，在肝HepG 2细胞中最高。槲皮素使表没食子儿茶素没食子酸酯（EGCG）在A549细胞中的细胞吸收增加了4倍，甲基化率从63%降低到19%;使表没食子儿茶素没食子酸酯在786-O细胞中的细胞吸收增加了2倍，甲基化率从97%降低到56%;与单独处理相比，组合显著降低了COMT的活性和蛋白表达，并降低了MRP 1的蛋白表达。该组合在A549细胞中表现出最强的抗增殖增加，在786-O细胞中表现出中等效果，在HepG 2细胞中表现出最低效果。槲皮素对GTP生物利用度和代谢的影响在体内得到证实。给SCID小鼠单独或联合服用冲泡绿色茶（GT）和补充0.4%槲皮素的饮食2周。我们观察到肺和肾中总的和非甲基化的EGCG增加了2至3倍，并且在肝脏中有增加的趋势。总之，结合槲皮素与GT提供了一个有前途的方法，以提高化学预防GT。不同的癌症的组合的反应可能会有所不同，取决于组织的内在COMT和MRP的活性。
The extensive methylation of green tea polyphenols (GTPs) in vivo may limit their chemopreventive potential. We investigated whether quercetin, a natural inhibitor of catechol-O-methyltransferase (COMT) and multidrug resistance proteins (MRPs), will differentially increase the intracellular concentration and decrease the methylation of GTPs in different cancer cell lines. Intrinsic COMT activity was lowest in lung cancer A549 cells, intermediate in kidney 786-O cells and highest in liver HepG2 cells. Quercetin increased the cellular absorption of epigallocatechin gallate (EGCG) four-fold in A549 cells with a decreased methylation rate from 63% to 19%, 2-fold in 786-O cells with a decreased methylation from 97% to 56%, while no significant effect was observed in HepG2 cells. The combination significantly decreased the activity and protein expression of COMT and decreased the protein expression of MRP1 compared to individual treatments. The combination exhibited the strongest increase in antiproliferation in A549 cells, an intermediate effect in 786-O cells and lowest effect in HepG2 cells. The effect of quercetin on bioavailability and metabolism of GTPs was confirmed in vivo. SCID mice were administered brewed green tea (GT) and a diet supplemented with 0.4% quercetin alone or in combination for 2 weeks. We observed a 2 to 3-fold increase of total and non-methylated EGCG in lung and kidney and a trend to increase in liver. In summary, combining quercetin with GT provides a promising approach to enhance the chemoprevention of GT. Responses of different cancers to the combination may vary by tissue depending on the intrinsic COMT and MRP activity.