Emetine exhibits anticancer activity in breast cancer cells as an antagonist of Wnt/β-catenin signaling

被引：22

作者：

Sun, Qi ^{[1
]}

Fu, Qiuxia ^{[1
]}

Li, Shiyue ^{[1
]}

Li, Junjun ^{[1
]}

Liu, Shanshan ^{[1
]}

Wang, Zhongyuan ^{[1
]}

Su, Zijie ^{[1
]}

Song, Jiaxing ^{[1
]}

Lu, Desheng ^{[1
]}

机构：

[1] Shenzhen Univ, Guangdong Key Lab Genome Stabil & Dis Prevent, Carson Int Canc Ctr, Dept Pharmacol,Hlth Sci Ctr, Shenzhen 518060, Guangdong, Peoples R China

来源：

ONCOLOGY REPORTS | 2019年 / 42卷 / 05期

关键词：

natural alkaloid; LRP6; DVL2; Wnt signaling; breast tumor; ALKALOID EMETINE; BETA-CATENIN; STEM-CELLS; PHASE-I; WNT; ACTIVATION; EXPRESSION; NSC-33669; APOPTOSIS; PHOSPHORYLATION;

D O I：

10.3892/or.2019.7290

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Emetine, an amoebicidal drug, exerts potent anticancer activity against various solid tumors, however, the underlying molecular mechanism remains unclear. In the present study, the effects of emetine were investigated on various proteins involved in the Wnt/beta-catenin signaling pathway, which has been linked to various human cancers. It was revealed that emetine blocked Wnt/beta-catenin signaling by targeting components of this pathway, including the low-density lipoprotein-receptor-related protein 6 (LRP6) and disheveled (DVL). Moreover, nanomolar concentrations of emetine decreased phosphorylation of these proteins and suppressed the expression of Wnt target genes, including fibronectin, frizzled-7 (Fzd7), c-Myc, Nanog and CD133 in MDA-MB-231 and MDA-MB-468 breast cancer cells. Additionally, emetine treatment induced apoptosis and suppressed the viability, migration, invasion, and sphere formation of breast cancer cells. Collectively the present results indicated that emetine antagonizes Wnt/beta-catenin signaling, providing insight into the molecular mechanism underlying the anticancer activity of emetine.

引用

页码：1735 / 1744

页数：10

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