STK295900, a Dual Inhibitor of Topoisomerase 1 and 2, Induces G(2) Arrest in the Absence of DNA Damage

PLoS One. 2013;8(1):e53908. doi: 10.1371/journal.pone.0053908. Epub 2013 Jan 22.

Abstract

STK295900, a small synthetic molecule belonging to a class of symmetric bibenzimidazoles, exhibits antiproliferative activity against various human cancer cell lines from different origins. Examining the effect of STK295900 in HeLa cells indicates that it induces G(2) phase arrest without invoking DNA damage. Further analysis shows that STK295900 inhibits DNA relaxation that is mediated by topoisomerase 1 (Top 1) and topoisomerase 2 (Top 2) in vitro. In addition, STK295900 also exhibits protective effect against DNA damage induced by camptothecin. However, STK295900 does not affect etoposide-induced DNA damage. Moreover, STK295900 preferentially exerts cytotoxic effect on cancer cell lines while camptothecin, etoposide, and Hoechst 33342 affected both cancer and normal cells. Therefore, STK295900 has a potential to be developed as an anticancer chemotherapeutic agent.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aniline Compounds / chemistry
  • Aniline Compounds / pharmacology*
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Benzimidazoles / chemistry
  • Benzimidazoles / pharmacology*
  • CDC2 Protein Kinase / metabolism
  • Camptothecin / pharmacology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • DNA Damage*
  • DNA Topoisomerases, Type I / metabolism*
  • DNA Topoisomerases, Type II / metabolism*
  • DNA, Neoplasm / genetics
  • DNA, Neoplasm / metabolism
  • Dose-Response Relationship, Drug
  • Etoposide / pharmacology
  • G2 Phase Cell Cycle Checkpoints / drug effects*
  • HCT116 Cells
  • HT29 Cells
  • HeLa Cells
  • Hep G2 Cells
  • Humans
  • Immunoblotting
  • MCF-7 Cells
  • Molecular Structure
  • Neoplasms / genetics
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Phosphorylation / drug effects
  • Topoisomerase Inhibitors / chemistry
  • Topoisomerase Inhibitors / pharmacology*

Substances

  • 4,4'-(3H,3'H-5,5'-bibenzimidazole-2,2'-diyl)dianiline
  • Aniline Compounds
  • Antineoplastic Agents, Phytogenic
  • Benzimidazoles
  • DNA, Neoplasm
  • Topoisomerase Inhibitors
  • Etoposide
  • CDC2 Protein Kinase
  • DNA Topoisomerases, Type I
  • DNA Topoisomerases, Type II
  • bisbenzimide ethoxide trihydrochloride
  • Camptothecin