期刊
JOURNAL OF NATURAL PRODUCTS
卷 70, 期 5, 页码 763-767出版社
AMER CHEMICAL SOC
DOI: 10.1021/np060609z
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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 dietay 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.
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