Zerumbone inhibits epithelial-mesenchymal transition and cancer stem cells properties by inhibiting the β-catenin pathway through miR-200c

J Cell Physiol. 2018 Dec;233(12):9538-9547. doi: 10.1002/jcp.26874. Epub 2018 Jun 26.

Abstract

Colorectal cancer (CRC) is one of the most lethal and rampant human malignancies in the world. Zerumbone, a sesquiterpene isolated from subtropical ginger, has been found to exhibit an antitumor effect in various cancer types. However, the effect of Zerumbone on the biological properties of CRC, including epithelial-mesenchymal transition (EMT) and cancer stem cells (CSCs) has not been fully elucidated. Here, we investigated the inhibitory action of Zerumbone on the EMT process, CSC markers, and the β-catenin signaling pathway in the presence or absence of miR-200c. The effect of Zerumbone on HCT-116 and SW-48 cells viability was examined by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay. The effects of Zerumbone on EMT-related genes, CSCs markers, cell migration, invasion, sphere-forming, and β-catenin signaling pathway were explored. To evaluate the role of miR-200c in anticancer effects by Zerumbone, miR-200c was downregulated by LNA-anti-miR-200c. Zerumbone significantly inhibited cell viability, migration, invasion, and sphere-forming potential in HCT-116 and SW-48 cell lines. Zerumbone significantly suppressed the EMT and CSC properties as well as downregulated the β-catenin. Silencing of miR200c reduced the inhibitory effects of Zerumbone on EMT and CSCs in CRC cells. These data indicated that Zerumbone may be a promising candidate for reducing the risk of CRC progression by suppressing the β-catenin pathway via miR-200c.

Keywords: Zerumbone; cancer stem cells (CSCs); epithelial-mesenchymal transition (EMT); β-catenin pathway.

Publication types

  • Research Support, Non-U.S. Gov't
  • Retracted Publication

MeSH terms

  • Biomarkers, Tumor / metabolism
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Survival / drug effects
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / pathology
  • Down-Regulation / drug effects
  • Down-Regulation / genetics
  • Epithelial-Mesenchymal Transition / drug effects*
  • Humans
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neoplasm Invasiveness
  • Neoplastic Stem Cells / drug effects
  • Neoplastic Stem Cells / metabolism*
  • Neoplastic Stem Cells / pathology*
  • Sesquiterpenes / pharmacology*
  • Spheroids, Cellular / drug effects
  • Spheroids, Cellular / metabolism
  • Spheroids, Cellular / pathology
  • Wnt Signaling Pathway / drug effects*
  • beta Catenin / metabolism*

Substances

  • Biomarkers, Tumor
  • MIRN200 microRNA, human
  • MicroRNAs
  • Sesquiterpenes
  • beta Catenin
  • zerumbone