Xanthatin mediates G2/M cell cycle arrest, autophagy and apoptosis via ROS/XIAP signaling in human colon cancer cells
Xanthatin mediates G2/M cell cycle arrest, autophagy and apoptosis via ROS/XIAP signaling in human colon cancer cells
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黄黄素通过人结肠癌细胞中的 ROS/XIAP 信号传导介导 G2/M 细胞周期停滞、自噬和凋亡
DOI：
10.1080/14786419.2018.1544976
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发表时间：
2020-09-16
影响因子：
2.2
通讯作者：
Shen, Ai-Zong
中科院分区：
文献类型：
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作者：
Geng, Ya-di;Zhang, Lei;Shen, Ai-Zong
黄苷是从菊科苍耳属植物中提取的一种天然植物双环倍半萜内酯，本研究首次证实黄苷对人结肠癌细胞的增殖有抑制作用，并可介导G（2）/M期阻滞。黄嘌呤还激活caspase并介导这些细胞的凋亡。同时，黄嘌呤触发细胞自噬反应。我们发现X-linked凋亡抑制蛋白（XIAP）的下调参与了细胞凋亡和自噬的诱导。此外，在结肠癌细胞中暴露于黄嘌呤后触发活性氧（ROS）产生。ROS抑制剂N-乙酰半胱氨酸（NAC）可显著逆转XIAP下调、G2/M期阻滞、细胞凋亡和自噬体积聚。总之，我们的研究结果表明，黄嘌呤导致人结肠癌细胞的G（2）/M期阻滞，并通过ROS/XIAP介导凋亡和自噬。我们为开发黄嘌呤作为一种有前途的抗肿瘤候选药物治疗结肠癌提供了分子基础。
Xanthatin is a natural plant bicyclic sesquiterpene lactone extracted fromXanthium plants (Asteraceae).In the present study, we demonstrated for the first time that Xanthatin inhibited cell proliferation and mediated G(2)/M phase arrest in human colon cancer cells. Xanthatin also activated caspase and mediated apoptosis in these cells. Concomitantly, Xanthatin triggered cell autophagic response. We found down-regulation of X-linked inhibitor of apoptosis protein (XIAP) contribute to the induction of apoptosis and autophagy. Moreover, reactive oxygen species (ROS) production was triggered upon exposure to Xanthatin in colon cancer cells. ROS inhibitor N-acetylcysteine (NAC) significantly reversed Xanthatin-mediated XIAP down-regulation, G(2)/M phase arrest, apoptosis and autophagosome accumulation. In summary, our findings demonstrated that Xanthatin caused G(2)/M phase arrest and mediated apoptosis and autophagy through ROS/XIAP in human colon cancer cells. We provided molecular bases for developing Xanthatin as a promising antitumor candidate for colon cancer therapy.