Yano Satoshi, Wu Shusong, Sakao Kozue, Hou De-Xing
a Course of Biological Science and Technology, United Graduate School of Agricultural Sciences , Kagoshima University , Kagoshima , Japan.
b Department of Animal Nutrition and Feed Science, College of Animal Science and Technology , Hunan Agricultural University , Changsha , China.
Biosci Biotechnol Biochem. 2019 May;83(5):960-969. doi: 10.1080/09168451.2019.1574206. Epub 2019 Feb 7.
6-(Methylsulfinyl)hexyl isothiocyanate (6-MSITC) is a major bioactive compound in Wasabi. Although 6-MSITC is reported to have cancer chemopreventive activities in rat model, the molecular mechanism is unclear. In this study, we investigated the anticancer mechanisms using two types of human colorectal cancer cells (HCT116 p53 and p53). 6-MSITC caused cell cycle arrest in G/M phase and induced apoptosis in both types of cells in the same fashion. Signaling data revealed that the activation of ERK1/2, rather than p53, is recruited for 6-MSITC-induced apoptosis. 6-MSITC stimulated ERK1/2 phosphorylation, and then activated ERK1/2 signaling including ELK1 phosphorylation, and upregulation of C/EBP homologous protein (CHOP) and death receptor 5 (DR5). The MEK1/2 inhibitor U0126 blocked all of these molecular events induced by 6-MSITC, and enhanced the cell viability in both types of cells in the same manner. These results indicated that ERK1/2-mediated ELK1/CHOP/DR5 pathway is involved in 6-MSITC-induced apoptosis in colorectal cancer cells. Abbreviations: CHOP: C/EBP homologous protein; DR5: death receptor 5; ELK1: ETS transcription factor; ERK1/2: extracellular signal-regulated kinase 1/2; JNK: Jun-N-terminal kinase; MAPK: mitogen-activated protein kinase; MEK1/2: MAP/ERK kinase 1/2; 6-MSITC: 6-(methylsulfinyl)hexyl isothiocyanate; MTT: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; PARP: poly(ADP-ribose) polymerase.
6-（甲基亚磺酰基）己基异硫氰酸酯（6-MSITC）是山葵中的一种主要生物活性化合物。尽管据报道6-MSITC在大鼠模型中具有癌症化学预防活性，但其分子机制尚不清楚。在本研究中，我们使用两种类型的人结肠癌细胞（HCT116 p53野生型和p53缺失型）研究了其抗癌机制。6-MSITC以相同方式导致两种类型的细胞在G/M期发生细胞周期停滞并诱导凋亡。信号数据显示，6-MSITC诱导的凋亡所涉及的是ERK1/2的激活，而非p53。6-MSITC刺激ERK1/2磷酸化，进而激活包括ELK1磷酸化、C/EBP同源蛋白（CHOP）和死亡受体5（DR5）上调在内的ERK1/2信号传导。MEK1/2抑制剂U0126阻断了6-MSITC诱导的所有这些分子事件，并以相同方式提高了两种类型细胞的活力。这些结果表明，ERK1/2介导的ELK1/CHOP/DR5途径参与了6-MSITC诱导的结肠癌细胞凋亡。缩写：CHOP：C/EBP同源蛋白；DR5：死亡受体5；ELK1：ETS转录因子；ERK1/2：细胞外信号调节激酶1/2；JNK：Jun氨基末端激酶；MAPK：丝裂原活化蛋白激酶；MEK1/2：MAP/ERK激酶1/2；6-MSITC：6-（甲基亚磺酰基）己基异硫氰酸酯；MTT：3-（4,5-二甲基噻唑-2-基）-2,5-二苯基四氮唑溴盐；PARP：聚（ADP-核糖）聚合酶 。
