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Cells lacking DNA topoisomerase II beta are resistant to genistein

Miguel López-Lazaro1, Elaine Willmore, Caroline A Austin

  • 1Institute for Cell and Molecular Biosciences, The Medical School, University of Newcastle-upon-Tyne, Newcastle-upon-Tyne, NE2 4HH, United Kingdom.

Journal of Natural Products
|April 7, 2007
PubMed

Insights

Dietary flavonoids genistein and luteolin impact DNA topoisomerases (topos). Genistein inhibits topoisomerase II (topo II), while luteolin inhibits topoisomerase I (topo I), suggesting roles in anticancer and carcinogenic effects.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Pharmacology

Background:

  • Flavonoids possess potential anticancer and carcinogenic properties.
  • DNA topoisomerases (topos) are implicated in these effects.
  • Genistein and luteolin are dietary flavonoids of interest.

Purpose of the Study:

  • To evaluate genistein and luteolin as DNA topoisomerase I (topo I) and topoisomerase II (topo II) poisons and catalytic inhibitors.
  • To investigate the role of topo II beta in genistein's cellular effects.

Main Methods:

  • Utilized the TARDIS cell-based assay in K562 leukemia cells.
  • Assessed topo I and topo II DNA complex formation.
  • Employed XTT and clonogenic assays to measure cell growth inhibition and cytotoxicity.
  • Examined genistein's effects in murine cells lacking topo II beta.

Main Results:

  • Genistein and luteolin induced topo II-DNA complexes, but not significant topo I-DNA complexes.
  • Genistein catalytically inhibited topo II, while luteolin inhibited topo I.
  • Cells lacking topo II beta were resistant to genistein's growth inhibition and cytotoxicity.
  • Genistein exposure led to high levels of topo II beta-DNA complexes.

Conclusions:

  • Topoisomerase II beta plays a crucial role in genistein-induced cell growth inhibition and death.
  • The study elucidates mechanisms by which genistein and luteolin interact with topoisomerases.
  • Findings contribute to understanding the dual role of flavonoids in cancer and carcinogenicity.

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