Lookup NU author(s): Dr Miguel Lopez-Lazaro,
Dr Elaine Willmore,
Professor Caroline Austin
Full text for this publication is not currently held within this repository. Alternative links are provided below where available.
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 IIβ were resistant to genistein-induced cell growth inhibition (XTT assays) and cytotoxicity (clonogenic assay). High levels of topo IIβ-DNA complexes were also observed in K562 cells exposed to genistein. These data suggest that topo IIβ 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. © 2007 American Chemical Society and American Society of Pharmacognosy.
Author(s): López-Lázaro, M., Willmore, E., Austin, C. A.
Publication type: Article
Publication status: Published
Journal: Journal of Natural Products
Print publication date: 01/05/2007
ISSN (print): 0163-3864
ISSN (electronic): 1520-6025
PubMed id: 17411092
Altmetrics provided by Altmetric