2-ethoxystypandrone, a novel small-molecule stat3 signaling inhibitor from polygonum cuspidatum, inhibits cell growth and induces apoptosis of hcc cells and hcc cancer stem cells
文献类型：期刊论文
| 作者 | Li, Wuguo1,3; Zhang, Qing2; Chen, Kaotan1; Sima, Zhenhua1; Liu, Jingli2; Yu, Qiang2; Liu, Jiawei1 |
| 刊名 | Bmc complementary and alternative medicine
 |
| 出版日期 | 2019-02-01 |
| 卷号 | 19页码:13 |
| ISSN号 | 1472-6882 |
| 关键词 | Polygonum cuspidatum 2-ethoxystypandrone Hepatocellular carcinoma Cancer stem cells Stat3 signaling pathway Cancer stemness inhibitor |
| DOI | 10.1186/s12906-019-2440-9 |
| 通讯作者 | Yu, qiang(qyu@sibs.ac.cn) ; Liu, jiawei(jiawei.liu@ymail.com) |
| 英文摘要 | Background: signal transducer and activator of transcription 3 (stat3) is an oncogene constitutively activated in hepatocellular carcinoma (hcc) cells and hcc cancer stem cells (cscs). constitutively activated stat3 plays a pivotal role in holding cancer stemness of hcc cscs, which are essential for hepatoma initiation, relapse, metastasis and drug resistance. therefore, stat3 has been validated as a novel anti-cancer drug target and the strategies targeting hcc cscs may bring new hopes to hcc therapy. this study aimed to isolate and identify small-molecule stat3 signaling inhibitors targeting cscs from the ethyl acetate (etoac) extract of the roots of polygonum cuspidatum and to evaluate their in vitro anti-cancer activities. methods: the chemical components of the etoac extract and the subfractions of p. cuspidatum were isolated by using various column chromatographies on silical gel, sephadex lh-20, and preparative hplc. their chemical structures were then determined on the basis of spectroscopic data including nmr, ms and ir analysis and their physicochemical properties. the inhibitory effects of the isolated compounds against stat3 signaling were screened by a stat3-dependent luciferase reporter gene assay. the tyrosine phosphorylation of stat3 was examined by western blot analysis. in vitro anti-cancer effects of the stat3 pathway inhibitor were further evaluated on cell growth of human hcc cells by a mtt assay, on self-renewal capacity of hcc cscs by the tumorsphere formation assay, and on cell cycle and apoptosis by flow cytometry analysis, respectively. results: the etoac extract of the roots of p. cuspidatum was investigated and a novel juglone analogue 2-ethoxystypandrone (1) along with seven known compounds (2-8) was isolated. among the eight isolated compounds 1-8, 2-ethoxystypandrone was a novel and potent stat3 signaling inhibitor (ic50=7.75 +/- 0.18 mu m), and inhibited the il-6-induced and constitutive activation of phosphorylation of stat3 in hcc cells. moreover, 2-ethoxystypandrone inhibited cell survival of hcc cells (ic50 = 3.69 +/- 0.51 mu m similar to 20.36 +/- 2.90 mu m), blocked the tumorspheres formation (ic50=2.70 +/- 0.28 mu m), and induced apoptosis of hcc cscs in a dose-dependent manner. conclusion: a novel juglone analogue 2-ethoxystypandrone was identified from the etoac extract of the roots of p. cuspidatum and was demonstrated to be a potent small-molecule stat3 signaling inhibitor, which strongly blocked stat3 activation, inhibited proliferation, and induced cell apoptosis of hcc cells and hcc cscs. 2-ethoxystypandrone as a stat3 signaling inhibitor might be a promising lead compound for further development into an anti-cscs drug. |
| WOS关键词 | LIVER ; PATHWAY ; 2-METHOXYSTYPANDRONE ; IDENTIFICATION ; TRANSDUCER ; ACTIVATOR ; JUGLONE ; KINASE |
| WOS研究方向 | Integrative & Complementary Medicine |
| WOS类目 | Integrative & Complementary Medicine |
| 语种 | 英语 |
| 出版者 | BMC |
| WOS记录号 | WOS:000457456300002 |
| URI标识 | http://www.irgrid.ac.cn/handle/1471x/2373187 |
| 专题 | 武汉病毒研究所 |
| 通讯作者 | Yu, Qiang; Liu, Jiawei |
| 作者单位 | 1.Guangzhou Univ Chinese Med, Higher Educ Mega Ctr, Res Ctr Med Plant Resource Sci & Engn, Minist Educ,Key Lab Chinese Med Resource Lingnan, 232 Waihuandong Rd, Guangzhou 510006, Guangdong, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Dept Pharmacol, 555 Chong Zhi Rd,Zhangjiang Hitech Pk, Shanghai 201203, Peoples R China 3.Sun Yat Sen Univ, Affiliated Hosp 1, Anim Expt Ctr, Guangzhou, Guangdong, Peoples R China |
| 推荐引用方式 GB/T 7714 | Li, Wuguo,Zhang, Qing,Chen, Kaotan,et al. 2-ethoxystypandrone, a novel small-molecule stat3 signaling inhibitor from polygonum cuspidatum, inhibits cell growth and induces apoptosis of hcc cells and hcc cancer stem cells[J]. Bmc complementary and alternative medicine,2019,19:13. |
| APA | Li, Wuguo.,Zhang, Qing.,Chen, Kaotan.,Sima, Zhenhua.,Liu, Jingli.,...&Liu, Jiawei.(2019).2-ethoxystypandrone, a novel small-molecule stat3 signaling inhibitor from polygonum cuspidatum, inhibits cell growth and induces apoptosis of hcc cells and hcc cancer stem cells.Bmc complementary and alternative medicine,19,13. |
| MLA | Li, Wuguo,et al."2-ethoxystypandrone, a novel small-molecule stat3 signaling inhibitor from polygonum cuspidatum, inhibits cell growth and induces apoptosis of hcc cells and hcc cancer stem cells".Bmc complementary and alternative medicine 19(2019):13. |
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来源：武汉病毒研究所
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