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

Abstract

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/β‑catenin signaling pathway, which has been linked to various human cancers. It was revealed that emetine blocked Wnt/β‑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/β‑catenin signaling, providing insight into the molecular mechanism underlying the anticancer activity of emetine.

• Authors: Qi Sun, Qiuxia Fu, Shiyue Li, Junjun Li, Shanshan Liu, Zhongyuan Wang, Zijie Su, Jiaxing Song, Desheng Lu
• Journal: Oncology reports (Oncol Rep) Vol. 42 Issue 5 Pg. 1735-1744 (Nov 2019) ISSN: 1791-2431 [Electronic] Greece
• PMID: 31436297 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents, Phytogenic
• Dishevelled Proteins
• LRP6 protein, human
• Low Density Lipoprotein Receptor-Related Protein-6
• Emetine

Topics

• Antineoplastic Agents, Phytogenic (pharmacology)
• Breast Neoplasms (drug therapy, genetics, metabolism)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Dishevelled Proteins (genetics, metabolism)
• Down-Regulation
• Drug Screening Assays, Antitumor
• Emetine (pharmacology)
• Female
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Low Density Lipoprotein Receptor-Related Protein-6 (genetics, metabolism)
• Wnt Signaling Pathway (drug effects)