title: Cells lacking DNA topoisomerase II beta are resistant to genistein.
abstract: Evidence suggests that DNA topoisomerases (topos) may be involved in the anticancer and carcinogenic properties attributed to flavonoids. Using the cell-based assay TARDIS, the dietary flavonoids genistein (1) and luteolin (2) have been evaluated as topo I and topo II poisons and catalytic inhibitors in K562 leukemia cells. Both flavonoids induced topo II-DNA complexes, but they did not induce significant levels of topo I-DNA complexes. Genistein decreased the topo II-DNA complexes induced by the topo II poison etoposide, suggestive of a catalytic inhibition of topo II, and luteolin decreased the topo I-DNA complexes induced by the topo I poison camptothecin, indicative of a catalytic inhibition of topo I. Murine transgenic cells lacking topo II beta were resistant to genistein-induced cell growth inhibition (XTT assays) and cytotoxicity (clonogenic assay). High levels of topo II beta-DNA complexes were also observed in K562 cells exposed to genistein. These data suggest that topo II beta has an important function in genistein-induced cell growth inhibition and cell death. The possible role of topoisomerases in the putative anticancer and carcinogenic properties of genistein and luteolin is discussed.
authors.affiliation: Institute for Cell and Molecular Biosciences, The Medical School, University of Newcastle-upon-Tyne, Newcastle-upon-Tyne, NE2 4HH, United Kingdom.
authors.forename: Miguel
authors.initials: M
authors.lastname: López-Lazaro
authors.forename: Elaine
authors.initials: E
authors.lastname: Willmore
authors.forename: Caroline A
authors.initials: CA
authors.lastname: Austin
mesh_terms: D000818:Animals; D004247:DNA / Q000737:chemistry*; D004264:DNA Topoisomerases, Type I / Q000172:deficiency / Q000378:metabolism; D004250:DNA Topoisomerases, Type II / Q000172:deficiency* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000172:deficiency* / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D019833:Genistein / Q000494:pharmacology*; D047311:Luteolin / Q000494:pharmacology; D051379:Mice; D015394:Molecular Structure
chemical_list: D004268:DNA-Binding Proteins; D004247:DNA; D019833:Genistein; D004264:DNA Topoisomerases, Type I; D004250:DNA Topoisomerases, Type II; D047311:Luteolin