Inhibitory effect of DNA topoisomerase inhibitor isoliquiritigenin on the growth of glioma cells

Int J Clin Exp Pathol. 2015 Oct 1;8(10):12577-82. eCollection 2015.

Abstract

Objective: To investigate the effect of isoliquiritigenin on the activity of DNA topoisomerase (TOP I) and its inhibitory effect on the growth of U87 glioma cells.

Methods: This study investigated the inhibitory effect of isoliquiritigenin on the growth of U87 glioma cells and its cytotoxicity by MTT method and determined the effect of isoliquiritigenin on TOP I activity by agarose gel electrophoresis. On this basis, we studied the interaction between isoliquiritigenin and TOP I and DNA. Finally, we further discussed the effect of isoliquiritigenin on the activity of Caspase 3, the apoptosis protein of U87 glioma cells.

Results: Isoliquiritigenin could inhibit the growth of U87 glioma cells (half inhibitory concentration IC50: 0.221 mM) and is of low cytotoxicity to normal cells. Agarose gel electrophoresis showed that isoliquiritigenin had significant inhibitory effect on TOP I activity. Molecular simulation results indicated that isoliquiritigenin took priority of binding to the active center of TOP I, and formed hydrogen bonds with the catalytic site Try723. Finally, Caspase 3 activity detection results suggested that isoliquiritigenin could significantly increase the activity of Caspase 3 (P < 0.05).

Conclusion: Isoliquiritigenin had a reversible inhibitory effect on TOP I activity, reduced the rate of single strand DNA unwinding in tumor cells, and thus played an important role in inducing the apoptosis of U87 glioma cells.

Keywords: DNA topoisomerase; Isoliquiritigenin; U87 glioma cell; apoptosis; inhibitory effect.

MeSH terms

  • Apoptosis / drug effects
  • Brain Neoplasms / pathology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Chalcones / pharmacology*
  • Electrophoresis, Agar Gel
  • Glioma / pathology*
  • Humans
  • Inhibitory Concentration 50
  • Molecular Docking Simulation
  • Topoisomerase Inhibitors / pharmacology*

Substances

  • Chalcones
  • Topoisomerase Inhibitors
  • isoliquiritigenin