Immunoprotective effect of epigallocatechin-3-gallate on oral anticancer drug-induced α-defensin reduction in Caco-2 cells.
Immunoprotective effect of epigallocatechin-3-gallate on oral anticancer drug-induced α-defensin reduction in Caco-2 cells.
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DOI：
10.1248/bpb.b13-00700
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发表时间：
2014-03
影响因子：
2
通讯作者：
N. Takahashi;Masaki Kobayashi;Jiro Ogura;Hiroaki Yamaguchi;T. Satoh;Kazuhiro Watanabe;K. Iseki
中科院分区：
文献类型：
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作者：
N. Takahashi;Masaki Kobayashi;Jiro Ogura;Hiroaki Yamaguchi;T. Satoh;Kazuhiro Watanabe;K. Iseki
以Caco-2细胞为模型，研究替加氟（FT）与表没食子儿茶素没食子酸酯（EGCG）相互作用对人α-防御素（HD-5：human α-defensin 5，HD-6：human α-defensin 6）表达的影响。这是首次研究口服抗癌药物和功能性食品对先天免疫系统的相互作用。α-防御素（α-Defensins）是人和小鼠潘氏细胞（Paneth cell）中的重要成分，在肠道天然免疫系统中发挥重要作用。我们检测了Caco-2细胞中HD-5和HD-6的mRNA水平，并评估了FT和EGCG对这些mRNA水平的影响。HD-5和HD-6 mRNA水平降低暴露于FT。暴露于FT以及H2 O2暴露诱导活性氧（ROS）的产生，并且EGCG抑制FT诱导的ROS产生。此外，FT诱导的HD-5和HD-6 mRNA水平的降低几乎完全被EGCG抑制。这些结果表明，EGCG在转录水平上恢复了FT诱导的Caco-2细胞α-防御素水平的下降，提示EGCG可作为化疗的辅助治疗。
The aim of this study was to determine the effect of interaction between tegafur (FT) and epigallocatechin-3-gallate (EGCG) on the expression of α-defensins (HD-5: human α-defensin 5, HD-6: human α-defensin 6) by using a Caco-2 cell line as a model of human intestinal epithelial cells. This is the first study in which the effect of interaction of an oral anticancer drug and functional food on the innate immune system was examined. α-Defensins are abundant constituents of mouse and human paneth cells and play a role in the innate immune system in intestine. We detected HD-5 and HD-6 mRNA in Caco-2 cells and evaluated the effects of FT and EGCG on these mRNA levels. HD-5 and HD-6 mRNA levels were decreased by exposure to FT. Production of reactive oxygen species (ROS) was induced by exposure to FT as well as H2O2 exposure, and EGCG suppressed FT-induced production of ROS. Furthermore, FT-induced decrease in HD-5 and HD-6 mRNA levels was almost completely suppressed by EGCG. These results indicate that EGCG restored the decrease of α-defensins induced by FT at the transcriptional level in Caco-2 cells, suggesting that EGCG can be used as adjunctive therapy in chemotherapy.