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

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

Author information

1
Department of Neurosurgery, The First Affiliated Hospital of Xinxiang Medical University Weihui 453100, Henan Province, China.
2
Department of Oncology, The First Affiliated Hospital of Xinxiang Medical University Weihui 453100, Henan Province, China.

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

PMID:
26722447
PMCID:
PMC4680392
[Indexed for MEDLINE]
Free PMC Article

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