Role of the ROS/AMPK signaling pathway in tetramethylpyrazine-induced apoptosis in gastric cancer cells.
Role of the ROS/AMPK signaling pathway in tetramethylpyrazine-induced apoptosis in gastric cancer cells.
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ROS/AMPK信号通路在四甲基吡嗪诱导胃癌细胞凋亡中的作用
DOI：
10.3892/ol.2013.1403
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发表时间：
2013-08
期刊：
影响因子：
2.9
通讯作者：
Shao J
中科院分区：
文献类型：
--
作者：
Yi B;Liu D;He M;Li Q;Liu T;Shao J
四甲基吡嗪（TMPZ）是从传统中草药甘草中提取的活性成分之一，许多研究表明它具有抗癌活性。然而，其在胃癌中的有效性及其细胞机制相对未知。本研究旨在探讨TMPZ对胃癌细胞株SGC 7901的作用。结果表明，高剂量TMPZ可通过激活腺苷酸活化蛋白激酶（AMPK），产生活性氧（ROS），抑制胃癌细胞的生长，诱导胃癌细胞凋亡。TMPZ诱导的细胞凋亡过程包括Bax转位、线粒体膜电位下降、细胞色素c释放、caspase-9和caspase-3激活等。这些事件中的每一个都被AMPK的药理学抑制剂化合物C抑制。据我们所知，这些结果首次证明TMPZ诱导胃癌细胞凋亡与ROS/AMPK通路的激活有关。AMPK激活通过线粒体凋亡途径诱导凋亡。此外，这些结果提高了TMPZ可能在胃癌中具有未来治疗作用的可能性。
Tetramethylpyrazine (TMPZ) is one of the active compounds extracted from the traditional Chinese medicinal herb Chuanxiong and several studies have shown it to possess anticancer properties. However, its effectiveness in gastric cancer and its cellular mechanisms are relatively unknown. The present study aimed to investigate the effect of TMPZ on SGC7901 cells, and it was demonstrated that a high dose of TMPZ inhibited cell viability and induced apoptosis by stimulating AMP-activated protein kinase (AMPK) through the generation of reactive oxygen species (ROS). Furthermore, TMPZ-induced apoptosis resulted in the sequential events beginning with the translocation of Bax, the collapse of mitochondrial membrane potential (ΔΨm), the release of cytochrome c and the activation of caspase-9 and -3. Each of these events was inhibited by compound C, a pharmacological inhibitor of AMPK. To the best of our knowledge, these results demonstrate for the first time that the induction of apoptosis by TMPZ in gastric cancer cells is associated with the activation of the ROS/AMPK pathway. AMPK activation induces apoptosis through the mitochondrial apoptotic pathway. In addition, these results raise the possibility that TMPZ may have a future therapeutic role in gastric cancer.
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