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

Oncol Rep. 2019 Nov;42(5):1735-1744. doi: 10.3892/or.2019.7290. Epub 2019 Aug 22.

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.

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Dishevelled Proteins / genetics
  • Dishevelled Proteins / 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
  • Low Density Lipoprotein Receptor-Related Protein-6 / metabolism
  • Wnt Signaling Pathway / drug effects*

Substances

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