Inhibition of the Proliferation and Invasion of C6 Glioma Cells by Tricin via the Upregulation of Focal-Adhesion-Kinase-Targeting MicroRNA-7

J Agric Food Chem. 2018 Jul 5;66(26):6708-6716. doi: 10.1021/acs.jafc.8b00604. Epub 2018 Jun 20.

Abstract

Tricin, a natural flavonoid present in large amounts in rice bran, was investigated for the mechanisms by which it exhibited antiproliferation and anti-invasion in C6 glioma cells. The results indicated that treatment with 5, 10, 25, and 50 μM tricin for 48 h significantly ( p < 0.05) inhibited cell numbers and colony numbers with values of 134.3 ± 5.5, 114.6 ± 2.5, 106.3 ± 3.2, and 57.3 ± 10.2, respectively. Tricin also inhibited C6-cell motility, migration, and invasion. Tricin changed the cytoskeletal organization, reduced matrix-metalloproteinase (MMP) expression, and upregulated E-cadherin. Tricin decreased FAK protein levels and suppressed focal-adhesion-kinase (FAK)-downstream-signal activation. Most importantly, tricin dose-dependently upregulated microRNA-7 (miR-7). Transfection with an miR-7 inhibitor suppressed miR-7 expression, increased FAK expression, and promoted the proliferation and invasion in C6 cells. The data support a novel anticancer mechanism of tricin that involves upregulation of FAK-targeting miR-7 in C6 glioma cells.

Keywords: anticancer; focal-adhesion kinase; glioma; microRNA-7; tricin.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Flavonoids / pharmacology*
  • Focal Adhesion Protein-Tyrosine Kinases / genetics*
  • Focal Adhesion Protein-Tyrosine Kinases / metabolism
  • Gene Expression Regulation, Neoplastic / drug effects
  • Glioma / drug therapy
  • Glioma / enzymology
  • Glioma / genetics
  • Glioma / physiopathology*
  • Humans
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neoplasm Invasiveness

Substances

  • Antineoplastic Agents
  • Flavonoids
  • MIRN7 microRNA, human
  • MicroRNAs
  • tricin
  • Focal Adhesion Protein-Tyrosine Kinases