4-Methylthio-3-butenyl isothiocyanate mediates nuclear factor (erythroid-derived 2)-like 2 activation by regulating reactive oxygen species production in human esophageal epithelial cells.
4-Methylthio-3-butenyl isothiocyanate mediates nuclear factor (erythroid-derived 2)-like 2 activation by regulating reactive oxygen species production in human esophageal epithelial cells.
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DOI：
10.1016/j.fct.2017.11.022
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发表时间：
2018
期刊：
影响因子：
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通讯作者：
T. Hirata;Young-Man Cho;Isamu Suzuki;T. Toyoda;Jun-ichi Akagi;Yasushi Nakamura;S. Numazawa;K. Ogawa
中科院分区：
文献类型：
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作者：
T. Hirata;Young-Man Cho;Isamu Suzuki;T. Toyoda;Jun-ichi Akagi;Yasushi Nakamura;S. Numazawa;K. Ogawa
从萝卜中提取的4-甲硫基-3-丁烯基异硫氰酸酯（MTBITC）具有抗突变性，可作为一种有效的化学预防剂应用于多种癌症的治疗，但相关机制的报道较少。我们调查是否MTBITC诱导细胞保护基因，包括II相酶，在Het-1A人食管上皮细胞。在用10 μM MTBITC处理的Het-1A细胞中，HMOX 1、NQO 1和GCLC mRNA水平以及核因子（红细胞衍生2）样2（Nrf 2）蛋白水平升高。MTBITC处理Het-1A细胞后，活性氧（ROS）趋于增加，而N-乙酰基-L-半胱氨酸处理则完全消除了MTBITC处理细胞中活性氧和Nrf 2表达的增加。我们还研究了Nrf 2激活和丝裂原活化蛋白激酶（MAPK）信号之间的关系，通过蛋白质印迹分析。MTBITC诱导Het-1A细胞中的细胞外信号调节激酶、c-Jun N-末端激酶和p38磷酸化;然而，MTBITC不影响Nrf 2激活和MAPK应答之间的关系。在本研究中，我们发现MTBITC通过在Het-1A细胞中产生ROS来诱导Nrf 2激活和细胞保护基因。这些结果表明，MTBITC可能有潜在的预防食管癌通过修改致癌物质代谢的第二阶段酶诱导通过ROS的生产。
4-Methylthio-3-butenyl isothiocyanate (MTBITC) extracted from daikon (Raphanus sativus), which shows antimutagenicity, may have applications as an effective chemopreventive agent in several cancers; however, few reports have described the associated mechanisms. We investigated whether MTBITC induced cytoprotective genes, including phase II enzymes, in Het-1A human esophageal epithelial cells. HMOX1,NQO1, and GCLC mRNA levels and nuclear factor (erythroid-derived 2)-like 2 (Nrf2) protein levels were increased in Het-1A cells treated with 10 μM MTBITC. Reactive oxygen species (ROS) tended to increase when Het-1A cells were treated with MTBITC, and the increases in ROS and Nrf2 expression in the cells treated with MTBITC were completely abolished by treatment withN-acetyl-l-cysteine. We also examined the relationships between Nrf2 activation and mitogen-activated protein kinase (MAPK) signaling by western blot analysis. MTBITC induced extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38 phosphorylation in Het-1A cells; however, MTBITC did not affect the relationship between Nrf2 activation and MAPK responses. In the present study, we found that MTBITC induced Nrf2 activation and cytoprotective genes via ROS production in Het-1A cells. These results suggest that MTBITC may have the potential for preventing esophageal carcinogenesis through modification of carcinogen metabolism by phase II enzyme induction via ROS production.