Adenanthin targets peroxiredoxin I/II to kill hepatocellular carcinoma cells.
Adenanthin targets peroxiredoxin I/II to kill hepatocellular carcinoma cells.
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Adenanthin 靶向过氧化还原蛋白 I/II 杀死肝细胞癌细胞
DOI：
10.1038/cddis.2014.345
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发表时间：
2014-09-04
影响因子：
9
通讯作者：
Chen GQ
中科院分区：
文献类型：
--
作者：
Hou JK;Huang Y;He W;Yan ZW;Fan L;Liu MH;Xiao WL;Sun HD;Chen GQ
阿德南素是一种从腺花香茶菜叶中分离出来的天然二萜类化合物，最近有报道称其通过靶向过氧化物氧还蛋白（Prx）I和II诱导白血病细胞分化。另一方面，越来越多的证据表明，这些Prx蛋白将成为筛选预防和治疗实体瘤药物的潜在靶点。因此，探讨腺嘌呤对实体瘤细胞的潜在作用具有重要意义。在这里，我们证明，Prx I蛋白是必不可少的肝细胞癌（HCC）细胞的生存，和腺嘌呤可以杀死这些恶性肝细胞在体外和异种移植。我们还表明，细胞死亡诱导活性的肝细胞癌细胞上的腺嘌呤是介导的活性氧（ROS）水平的增加。此外，Prx I或Prx II的沉默显著增强了腺嘌呤对HCC的细胞毒性活性，而Prx I和Prx II的异位表达而不是它们的腺嘌呤结合半胱氨酸突变体可以在Prxs沉默的HCC细胞中拯救腺嘌呤诱导的细胞毒性。综上所述，我们的研究结果表明，腺嘌呤靶向Prx I/II杀死肝癌细胞，其治疗意义值得进一步探讨在肝癌患者。
Adenanthin, a natural diterpenoid isolated from the leaves of Isodon adenanthus, has recently been reported to induce leukemic cell differentiation by targeting peroxiredoxins (Prx) I and II. On the other hand, increasing lines of evidence propose that these Prx proteins would become potential targets to screen drugs for the prevention and treatment of solid tumors. Therefore, it is of significance to explore the potential activities of adenanthin on solid tumor cells. Here, we demonstrate that Prx I protein is essential for the survival of hepatocellular carcinoma (HCC) cells, and adenanthin can kill these malignant liver cells in vitro and xenografts. We also show that the cell death-inducing activity of adenanthin on HCC cells is mediated by the increased reactive oxygen species (ROS) levels. Furthermore, the silencing of Prx I or Prx II significantly enhances the cytotoxic activity of adenanthin on HCC, whereas the ectopic expression of Prx I and Prx II but not their mutants of adenanthin-bound cysteines can rescue adenanthin-induced cytotoxicity in Prxs-silenced HCC cells. Taken together, our results propose that adenanthin targets Prx I/II to kill HCC cells and its therapeutic significance warrants to be further explored in HCC patients.