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Abstract：
BACKGROUND: Previous studies have presented evidence to support the significant association between red meat intake and colon cancer, suggesting that heme iron plays a key role in colon carcinogenesis. Epigallocatechin-3-gallate (EGCG), the major constituent of green tea, exhibits anti-oxidative and anti-cancer effects. However, the effect of EGCG on red meat-associated colon carcinogenesis is not well understood.
OBJECTIVE: We aimed to investigate the regulatory effects of hemin and EGCG on colon carcinogenesis and the underlying mechanism of action.
METHODS: Hemin and EGCG were treated in Caco2 cells to perform the water-soluble tetrazolium salt-1 assay, lactate dehydrogenase release assay, reactive oxygen species (ROS) detection assay, real-time quantitative polymerase chain reaction and western blot. We investigated the regulatory effects of hemin and EGCG on an azoxymethane (AOM) and dextran sodium sulfate (DSS)-induced colon carcinogenesis mouse model.
RESULTS: In Caco2 cells, hemin increased cell proliferation and the expression of cell cycle regulatory proteins, and ROS levels. EGCG suppressed hemin-induced cell proliferation and cell cycle regulatory protein expression as well as mitochondrial ROS accumulation. Hemin increased nuclear factor erythroid-2-related factor 2 (Nrf2) expression, but decreased Keap1 expression. EGCG enhanced hemin-induced Nrf2 and antioxidant gene expression. Nrf2 inhibitor reversed EGCG reduced cell proliferation and cell cycle regulatory protein expression. In AOM/DSS mice, hemin treatment induced hyperplastic changes in colon tissues, inhibited by EGCG supplementation. EGCG reduced the hemin-induced numbers of total aberrant crypts and malondialdehyde concentration in the AOM/DSS model.
CONCLUSIONS: We demonstrated that EGCG reduced hemin-induced proliferation and colon carcinogenesis through Nrf2-inhibited mitochondrial ROS accumulation.
OBJECTIVE: We aimed to investigate the regulatory effects of hemin and EGCG on colon carcinogenesis and the underlying mechanism of action.
METHODS: Hemin and EGCG were treated in Caco2 cells to perform the water-soluble tetrazolium salt-1 assay, lactate dehydrogenase release assay, reactive oxygen species (ROS) detection assay, real-time quantitative polymerase chain reaction and western blot. We investigated the regulatory effects of hemin and EGCG on an azoxymethane (AOM) and dextran sodium sulfate (DSS)-induced colon carcinogenesis mouse model.
RESULTS: In Caco2 cells, hemin increased cell proliferation and the expression of cell cycle regulatory proteins, and ROS levels. EGCG suppressed hemin-induced cell proliferation and cell cycle regulatory protein expression as well as mitochondrial ROS accumulation. Hemin increased nuclear factor erythroid-2-related factor 2 (Nrf2) expression, but decreased Keap1 expression. EGCG enhanced hemin-induced Nrf2 and antioxidant gene expression. Nrf2 inhibitor reversed EGCG reduced cell proliferation and cell cycle regulatory protein expression. In AOM/DSS mice, hemin treatment induced hyperplastic changes in colon tissues, inhibited by EGCG supplementation. EGCG reduced the hemin-induced numbers of total aberrant crypts and malondialdehyde concentration in the AOM/DSS model.
CONCLUSIONS: We demonstrated that EGCG reduced hemin-induced proliferation and colon carcinogenesis through Nrf2-inhibited mitochondrial ROS accumulation.
摘要：
背景：以前的研究已经提供了支持红肉摄入与结肠癌之间显著关联的证据，表明血红素铁在结肠癌的发生中起关键作用。表没食子儿茶素-3-没食子酸酯（EGCG），绿茶的主要成分，表现出抗氧化和抗癌作用。然而,EGCG对红肉相关结肠癌发生的影响尚不清楚.
目的：我们旨在研究血红素和EGCG对结肠癌发生的调节作用及其潜在的作用机制。
方法：在Caco2细胞中处理Hemin和EGCG以进行水溶性四唑鎓盐-1测定，乳酸脱氢酶释放试验，活性氧（ROS）检测试验，实时定量聚合酶链反应和蛋白质印迹。我们研究了血红素和EGCG对偶氮甲烷（AOM）和葡聚糖硫酸钠（DSS）诱导的结肠癌发生小鼠模型的调节作用。
结果：在Caco2细胞中，血红素增加细胞增殖和细胞周期调节蛋白的表达，和ROS水平。EGCG抑制血红素诱导的细胞增殖和细胞周期调节蛋白表达以及线粒体ROS积累。Hemin增加了核因子-2相关因子2（Nrf2）的表达，但降低Keap1表达。EGCG增强血红素诱导的Nrf2和抗氧化基因表达。Nrf2抑制剂逆转EGCG降低细胞增殖和细胞周期调控蛋白表达。在AOM/DSS小鼠中，血红素治疗引起结肠组织增生改变，通过补充EGCG抑制。EGCG减少了AOM/DSS模型中血红素诱导的总异常隐窝数量和丙二醛浓度。
结论：我们证明了EGCG通过Nrf2抑制线粒体ROS积累减少了血红素诱导的增殖和结肠癌的发生。
目的：我们旨在研究血红素和EGCG对结肠癌发生的调节作用及其潜在的作用机制。
方法：在Caco2细胞中处理Hemin和EGCG以进行水溶性四唑鎓盐-1测定，乳酸脱氢酶释放试验，活性氧（ROS）检测试验，实时定量聚合酶链反应和蛋白质印迹。我们研究了血红素和EGCG对偶氮甲烷（AOM）和葡聚糖硫酸钠（DSS）诱导的结肠癌发生小鼠模型的调节作用。
结果：在Caco2细胞中，血红素增加细胞增殖和细胞周期调节蛋白的表达，和ROS水平。EGCG抑制血红素诱导的细胞增殖和细胞周期调节蛋白表达以及线粒体ROS积累。Hemin增加了核因子-2相关因子2（Nrf2）的表达，但降低Keap1表达。EGCG增强血红素诱导的Nrf2和抗氧化基因表达。Nrf2抑制剂逆转EGCG降低细胞增殖和细胞周期调控蛋白表达。在AOM/DSS小鼠中，血红素治疗引起结肠组织增生改变，通过补充EGCG抑制。EGCG减少了AOM/DSS模型中血红素诱导的总异常隐窝数量和丙二醛浓度。
结论：我们证明了EGCG通过Nrf2抑制线粒体ROS积累减少了血红素诱导的增殖和结肠癌的发生。
