Cardiac Glycoside Ouabain Exerts Anticancer Activity via Downregulation of STAT3.
Cardiac Glycoside Ouabain Exerts Anticancer Activity via Downregulation of STAT3.
复制标题
强心苷哇巴因通过下调 STAT3 发挥抗癌活性
DOI：
10.3389/fonc.2021.684316
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发表时间：
2021
影响因子：
4.7
通讯作者：
Zhou M
中科院分区：
文献类型：
--
作者：
Du J;Jiang L;Chen F;Hu H;Zhou M
强心苷类化合物是一种植物源性甾体类化合物，已被用于治疗心血管疾病。哇巴因是一种强心类固醇和特异性Na+/K+-ATP酶抑制剂，已被重新发现用于治疗癌症。然而，哇巴因在各种癌症中的细胞靶点和抗癌机制仍然在很大程度上未被探索。在这项研究中，我们证实了哇巴因对几种癌细胞系的细胞毒作用。进一步的检测显示哇巴因处理诱导的细胞凋亡、细胞内活性氧产生和DNA双链断裂增加。此外，哇巴因除了阻断STAT 3介导的转录和下游靶蛋白外，还有效地抑制STAT 3的表达以及磷酸化。有趣的是，这些抑制活性似乎是独立的Na+/K+-ATP酶。此外，我们发现哇巴因通过调节真核起始因子4 E（eIF 4 E）和eIF 4 E结合蛋白1（4 EBP 1）来抑制蛋白质合成。本研究为哇巴因抗肿瘤作用的分子机制提供了新的思路，为强心苷类药物的合理应用提供了新的思路。
Cardiac glycosides are plant-derived steroid-like compounds which have been used for the treatment of cardiovascular diseases. Ouabain, a cardiotonic steroid and specific Na+/K+-ATPase inhibitor, has been rediscovered for its potential use in the treatment of cancer. However, the cellular targets and anticancer mechanism of ouabain in various cancers remain largely unexplored. In this study, we confirmed the cytotoxic effects of ouabain on several cancer cell lines. Further examination revealed the increase of apoptosis, intracellular ROS generation and DNA double-strand breaks induced by ouabain treatment. Besides, ouabain effectively suppressed STAT3 expression as well as phosphorylation in addition to block STAT3-mediated transcription and downstream target proteins. Interestingly, these inhibitory activities seemed to be independent of the Na+/K+-ATPase. Furthermore, we found that ouabain inhibited protein synthesis through regulation of the eukaryotic initiation factor 4E (eIF4E) and eIF4E binding protein 1 (4EBP1). Taken together, our study provided a novel molecular insight of anticancer activities of ouabain in human cancer cells, which could raise the hope of using cardiac glycosides for cancer therapeutics more rational.
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DOI：
10.1111/j.1365-2613.2010.00734.x
发表时间：
2010-12-01
影响因子：
3
作者：
Barry, Sean P.;Townsend, Paul A.;Stephanou, Anastasis
通讯作者：
Stephanou, Anastasis
影响因子：
3.7
作者：
Jun DW;Hwang M;Kim HJ;Hwang SK;Kim S;Lee CH
通讯作者：
Lee CH
影响因子：
4.6
作者：
Rasheduzzaman, Mohammad;Yin, Honghua;Park, Sang-Youel
通讯作者：
Park, Sang-Youel
影响因子：
4
作者：
Cavalcante-Silva LHA;Lima ÉA;Carvalho DCM;de Sales-Neto JM;Alves AKA;Galvão JGFM;da Silva JSF;Rodrigues-Mascarenhas S
通讯作者：
Rodrigues-Mascarenhas S
DOI：
10.1073/pnas.0907054106
发表时间：
2009-08-18
影响因子：
11.1
作者：
Ogawa, Haruo;Shinoda, Takehiro;Toyoshima, Chikashi
通讯作者：
Toyoshima, Chikashi