4-Methylthio-3-butenyl isothiocyanate (MTBITC) induced apoptotic cell death and G2/M cell cycle arrest via ROS production in human esophageal epithelial cancer cells
4-Methylthio-3-butenyl isothiocyanate (MTBITC) induced apoptotic cell death and G2/M cell cycle arrest via ROS production in human esophageal epithelial cancer cells
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DOI：
10.2131/jts.44.73
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发表时间：
2019-01-01
影响因子：
2
通讯作者：
Ogawa, Kumiko
中科院分区：
文献类型：
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作者：
Hirata, Tadashi;Cho, Young-Man;Ogawa, Kumiko
为了探讨4-甲硫基-3-丁烯基异硫氰酸酯(MTBITC)的化学预防机制，我们分析了MTBITC处理的KYSE510细胞在加入和不加入活性氧自由基(ROS)清除剂N-乙乙基-L-半胱氨酸(NAC)的情况下，细胞存活率、细胞周期分布、细胞周期和凋亡相关蛋白的表达水平。MTBITC剂量依赖性地降低细胞存活率和BC12蛋白的表达，同时诱导caspase-3、caspase-9和PARP-1的裂解，提示KYSE510细胞的细胞存活率降低是通过线粒体凋亡途径发生的。在细胞周期分布分析中，MTBITC(20-40 mU/M)诱导细胞周期停滞于G2/M期。此外，MTBITC还可诱导Chk1和Akt的磷酸化，并降低p27蛋白的表达。NAC可消除MTBITC诱导的细胞凋亡和细胞周期相关改变。这些结果表明，MTBITC通过诱导线粒体凋亡细胞死亡、G2/M细胞周期停滞和ROS的产生来消除癌细胞，从而具有化学预防食道癌发生的潜力。
To investigate the chemopreventive mechanisms of 4-Methylthio-3-butenyl isothiocyanate (MTBITC), we analyzed cell viability, cell cycle distribution, and expression levels for cell cycle and apoptosis-related proteins in MTBITC-treated malignant esophageal KYSE510 cells, with and without the reactive oxygen species (ROS) scavenger N-acethyl-L-Cysteine (NAC). MTBITC dose-dependently reduced cell viability and Bc12 protein expression, while it induced cleavages of caspase-3, caspase-9, and PARP-1, suggesting that reduced cell viability occurred through the mitochondrial apoptotic pathway in KYSE510 cells. In cell cycle distribution analysis, MTBITC (20-40 mu M) induced cell cycle arrest at G2/M phase. Furthermore, MTBITC induced Chkl and Akt phosphorylations and decreased p27 protein expression. Both apoptotic- and cell cycle-related changes induced by MTBITC treatment were abolished by NAC. These results suggest that MTBITC has chemopreventive potential for esophageal carcinogenesis by elimination of cancer cells via induction of mitochondrial apoptotic cell death, G2/M cell cycle arrest, and ROS production.