Identification of a small-molecule inhibitor of DNA topoisomerase II by proteomic profiling

Chem Biol. 2011 Jun 24;18(6):743-51. doi: 10.1016/j.chembiol.2011.03.012.


BNS-22, a chemically synthesized derivative of the natural plant product GUT-70, has antiproliferative activity against human cancer cells, the mechanism of which is unknown. Here, we identify a target of BNS-22 by proteomic profiling analysis, which suggests that BNS-22 belongs to the same cluster as ICRF-193, a DNA topoisomerase II (TOP2) catalytic inhibitor. BNS-22 inhibits kinetoplast DNA decatenation that is mediated by human TOP2α and TOP2β in vitro at an IC(50) of 2.8 and 0.42 μM, respectively. BNS-22 does not affect DNA damage and antagonizes TOP2 poison-mediated DNA damage. Like ICRF-193, BNS-22 induces mitotic abnormalities, characterized by impairments in chromosome alignment and segregation, thereby causing polyploidy in HeLa cells. These results indicate that BNS-22 targets TOP2 and acts as its catalytic inhibitor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cluster Analysis
  • Coumarins / chemistry*
  • Coumarins / toxicity
  • DNA Topoisomerases, Type II / chemistry*
  • DNA Topoisomerases, Type II / metabolism
  • Electrophoresis, Gel, Two-Dimensional
  • HeLa Cells
  • Humans
  • Proteome / metabolism*
  • Proteomics / methods
  • Quinolines / chemistry*
  • Quinolines / toxicity
  • Spindle Apparatus / drug effects
  • Structure-Activity Relationship
  • Topoisomerase II Inhibitors / chemistry*
  • Topoisomerase II Inhibitors / toxicity


  • BNS 22
  • Coumarins
  • Proteome
  • Quinolines
  • Topoisomerase II Inhibitors
  • DNA Topoisomerases, Type II