Inhibitory effect of galangin on DNA topoisomerases in lung cancer cells.
10.11817/j.issn.1672-7347.2015.05.004
- Author:
Xin ZHAO
1
;
Jian ZHANG
Author Information
1. Department of Respiration, Xinxiang Medical University, Xinxiang Henan 453000, China 507783645@qq.com.
- Publication Type:Journal Article
- MeSH:
Apoptosis;
Cell Cycle;
Cell Line, Tumor;
drug effects;
Cell Proliferation;
DNA Topoisomerases, Type I;
metabolism;
Flavonoids;
chemistry;
Humans;
Lung Neoplasms;
enzymology;
Topoisomerase Inhibitors;
chemistry
- From:
Journal of Central South University(Medical Sciences)
2015;40(5):479-485
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To explore the eff ect of galangin on DNA topoisomerases in lung cancer cells A549 and H46 as well on cell growth.
METHODS:The inhibitory effect of galangin on the growth of A549 and H46 cells was analyzed by MTT method. The effect of galangin on Topo I activity was detected by the agarose gel electrophoresis method. Furthermore, the interaction between galangin and Topo I was evaluated by fluorescence spectroscopy. Finally, the eff ect of galangin on the Topo I structure was discussed.
RESULTS:Galangin could induce the apoptosis of A549 and H46 cells (IC50 was 0.221 mmol/L and 0.173 mmol/L, respectively). Agarose gel electrophoresis showed that galangin exerted significant inhibitory effect on Topo I activity. Fluorescence spectrum analysis showed that galangin was able to quench Topo I fluorescence, and hydrophobic interaction was the main driving force. Circular dichroism analysis showed that galangin induced Topo I conformation change and increased the content of α-helix, which prevented the formation of active center and in turn led to the decrease in Topo I activity. Molecular simulation results showed that galangin could bind to the active center of Topo I to form hydrogen bonds with the catalytic site at Arg364 and Asn352.
CONCLUSION:Galangin is able to inhibit Topo I activity and to reduce the unwinding rate of single stranded DNNA in tumor cells, which plays an important role in induction of A549 and H46 cell apoptosis.
