I3C and ICZ inhibit migration by suppressing the EMT process and FAK expression in breast cancer cells

Mol Med Rep. 2013 Feb;7(2):384-8. doi: 10.3892/mmr.2012.1198. Epub 2012 Nov 23.

Abstract

Indole-3-carbinol (I3C) and indole[3,2-b] carbazole (ICZ) are major bioactive food components in cruciferous vegetables. Although previous studies have demonstrated the anticancer activity of I3C and ICZ in various types of cancer cells, the manner in which indole compounds regulate migration or related epithelial-to-mesenchymal transitions (EMT) has yet to be determined. In this study, we investigated the effects of I3C and ICZ on migration using breast cancer cells (MCF-7 and MDA-MB231). Pre‑treatment with I3C and ICZ significantly inhibited the migration of breast cancer cells without cytotoxicity, as measured by monolayer scratch assay. In addition, I3C and ICZ decreased vimentin (a mesenchymal marker) and focal adhesion kinase (FAK) mRNA expression, while increasing E-cadherin (an epithelial marker) expression. Matrix metalloproteinase (MMP)-2 and -9 activity was also reduced by I3C and ICZ. Taken together, we propose that I3C and ICZ pre‑treatment inhibits the migration of breast cancer cells through suppression of the EMT process and reduced MMP activity by repressing FAK expression. Our findings suggested that I3C and ICZ are potential compounds for inhibition of breast cancer cell migration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cadherins / genetics
  • Cadherins / metabolism
  • Carbazoles / chemistry
  • Carbazoles / pharmacology*
  • Cell Line, Tumor
  • Cell Movement / drug effects*
  • Cell Survival / drug effects
  • Epithelial-Mesenchymal Transition / drug effects*
  • Focal Adhesion Protein-Tyrosine Kinases / genetics
  • Focal Adhesion Protein-Tyrosine Kinases / metabolism
  • Humans
  • Indoles / chemistry
  • Indoles / pharmacology*
  • MCF-7 Cells
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • RNA, Messenger / metabolism
  • Vimentin / genetics
  • Vimentin / metabolism

Substances

  • Cadherins
  • Carbazoles
  • Indoles
  • RNA, Messenger
  • Vimentin
  • indolo(3,2-b)carbazole
  • indole-3-carbinol
  • Focal Adhesion Protein-Tyrosine Kinases
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9