Lněničková Kateřina, Procházková Eliška, Skálová Lenka, Matoušková Petra, Bártíková Hana, Souček Pavel, Szotáková Barbora
Department of Biochemical Sciences, Faculty of Pharmacy, Charles University, Hradec Králové CZ-50005, Czech Republic.
Toxicogenomics Unit, Centre of Toxicology and Health Safety, National Institute of Public Health, Prague CZ-10042, Czech Republic.
Molecules. 2016 Sep 7;21(9):1186. doi: 10.3390/molecules21091186.
The knowledge of processes in intestinal cells is essential, as most xenobiotics come into contact with the small intestine first. Caco-2 cells are human colorectal adenocarcinoma that once differentiated, exhibit enterocyte-like characteristics. Our study compares activities and expressions of important conjugation enzymes and their modulation by green tea extract (GTE) and epigallocatechin gallate (EGCG) using both proliferating (P) and differentiated (D) caco-2 cells. The mRNA levels of the main conjugation enzymes were significantly elevated after the differentiation of Caco-2 cells. However, no increase in conjugation enzymes' activities in differentiated cells was detected in comparison to proliferating ones. GTE/EGCG treatment did not affect the mRNA levels of any of the conjugation enzymes tested in either type of cells. Concerning conjugation enzymes activities, GTE/EGCG treatment elevated glutathione S-transferase (GST) activity by approx. 30% and inhibited catechol-O-methyltransferase (COMT) activity by approx. 20% in differentiated cells. On the other hand, GTE as well as EGCG treatment did not significantly affect the activities of conjugation enzymes in proliferating cells. Administration of GTE/EGCG mediated only mild changes of GST and COMT activities in enterocyte-like cells, indicating a low risk of GTE/EGCG interactions with concomitantly administered drugs. However, a considerable chemo-protective effect of GTE via the pronounced induction of detoxifying enzymes cannot be expected as well.
由于大多数外源性物质首先与小肠接触，了解肠道细胞中的过程至关重要。Caco-2细胞是人类结肠腺癌细胞，一旦分化，就会表现出类似肠上皮细胞的特征。我们的研究使用增殖型（P）和分化型（D）Caco-2细胞，比较了重要结合酶的活性和表达，以及绿茶提取物（GTE）和表没食子儿茶素没食子酸酯（EGCG）对它们的调节作用。Caco-2细胞分化后，主要结合酶的mRNA水平显著升高。然而，与增殖细胞相比，未检测到分化细胞中结合酶活性的增加。GTE/EGCG处理对两种类型细胞中所测试的任何结合酶的mRNA水平均无影响。关于结合酶活性，GTE/EGCG处理使分化细胞中的谷胱甘肽S-转移酶（GST）活性提高了约30%，并使儿茶酚-O-甲基转移酶（COMT）活性降低了约20%。另一方面，GTE和EGCG处理对增殖细胞中结合酶的活性均无显著影响。GTE/EGCG的给药仅使类肠上皮细胞中GST和COMT的活性发生轻微变化，表明GTE/EGCG与同时给药药物相互作用的风险较低。然而，也不能期望GTE通过显著诱导解毒酶而产生显著的化学保护作用。
