title: [Inhibitory effect of galangin on DNA topoisomerases in lung cancer cells].
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Respiration, Xinxiang Medical University, Xinxiang Henan 453000, China 507783645@qq.com.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhao
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
mesh_terms: D017209:Apoptosis; D002453:Cell Cycle; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation; D004264:DNA Topoisomerases, Type I / Q000378:metabolism*; D005419:Flavonoids / Q000737:chemistry*; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology*; D059003:Topoisomerase Inhibitors / Q000737:chemistry*
chemical_list: D005419:Flavonoids; D059003:Topoisomerase Inhibitors; C037032:galangin; D004264:DNA Topoisomerases, Type I; C528909:TOP1 protein, human