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Cells lacking DNA topoisomerase IIβ are resistant to genistein

Lookup NU author(s): Dr Miguel Lopez-Lazaro, Dr Elaine Willmore, Professor Caroline Austin

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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 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.


Publication metadata

Author(s): López-Lázaro, M., Willmore, E., Austin, C. A.

Publication type: Article

Publication status: Published

Journal: Journal of Natural Products

Year: 2007

Volume: 70

Issue: 5

Pages: 763-767

Print publication date: 01/05/2007

ISSN (print): 0163-3864

ISSN (electronic): 1520-6025

URL: http://dx.doi.org/10.1021/np060609z

DOI: 10.1021/np060609z

PubMed id: 17411092


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