Esculentoside H inhibits colon cancer cell migration and growth through suppression of MMP-9 gene expression via NF-kB signaling pathway

J Cell Biochem. 2019 Jun;120(6):9810-9819. doi: 10.1002/jcb.28261. Epub 2018 Dec 7.

Abstract

A water-soluble saponin, Esculentoside H (EsH), 3-O-(O-β-d-glucopyranosyl-(1→4)-β-d-xylopyranosyl)-28-β-d-glucopyranosylphytolaccagenin has been isolated and purified from the root extract of perennial plant Phytolacca esculenta. EsH is known to be an anticancer compound, having a capacity for TNF-α release. However, the effects of EsH on migration and growth in tumor cells have not yet been reported. In the current study, the suppressive effects of EsH on phorbol 12-myristate 13-acetate (PMA)-induced cell migration were examined in murine colon cancer CT26 cells and human colon cancer HCT116 cells. Interestingly, the transwell assay and wound healing show that EsH suppresses the PMA-induced migration and growth potential of HCT116 and CT26 colon cancer cells, respectively. EsH dose-dependently suppressed matrix metalloproteinases-9 (MMP-9) expression that was upregulated upon PMA treatment in messenger RNA levels and protein secretion. Since the expression of MMP-9 is correlated with nuclear factor-κB (NF-κB) signaling, it has been examined whether EsH inhibits PMA-induced IκB phosphorylation that leads to the suppression of NK-κB nuclear translocation. EsH repressed the phosphorylation level of JNK, but not extracellular signal-regulated kinase and p38 signaling when the cells were treated with PMA. Overall, these results demonstrated that EsH could suppress cancer migration through blockage of the JNK1/2 and NF-κB signaling-mediated MMP-9 expression.

Keywords: cancer; cancer growth; colon cancer; migration; mitogen-activated protein kinase-9.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Movement / drug effects*
  • Colonic Neoplasms
  • Gene Expression Regulation, Enzymologic / drug effects*
  • Gene Expression Regulation, Neoplastic / drug effects*
  • HCT116 Cells
  • Humans
  • MAP Kinase Signaling System / drug effects*
  • Male
  • Matrix Metalloproteinase 9 / biosynthesis*
  • Mice
  • Mice, Inbred BALB C
  • NF-kappa B / metabolism*
  • Neoplasm Proteins / metabolism*
  • Oleanolic Acid / analogs & derivatives*
  • Oleanolic Acid / pharmacology
  • Saponins / pharmacology*

Substances

  • NF-kappa B
  • Neoplasm Proteins
  • Saponins
  • esculentoside H
  • Oleanolic Acid
  • MMP9 protein, human
  • Matrix Metalloproteinase 9