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Selenite induces topoisomerase I and II-DNA complexes in K562 leukemia cells
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Dr Miguel Lopez-Lazaro
Dr Elaine Willmore
Dr Sarah Johnson
Professor Caroline Austin
López-Lázaro M, Willmore E, Elliott SL, Austin CA
International Journal of Cancer
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The essential trace element selenium is one of the most promising cancer chemopreventive agents. Data from preclinical studies have revealed that selenite, an inorganic form of selenium, may also be useful in cancer chemotherapy. DNA topoisomerases (topos) are the target of several useful anticancer drugs. These drugs induce DNA complexes with either topo I or topo II; then cellular processing coverts these topo-DNA complexes into permanent DNA strand breaks that ultimately lead to cell death. Previous reports have revealed that selenite can induce apoptosis in cancer cells selectively and that selenite-induced apoptosis is preceded by the formation of DNA strand breaks. In vitro experiments have shown that selenite induces topo II-DNA complexes, which seem to be involved in selenite-induced apoptosis. Using the cell-based assay TARDIS, here we show that selenite induces topo II-DNA complexes (topo IIalpha and topo IIbeta) in K562 leukemia cells; these complexes appeared in a time-dependent manner and correlated with the induction of apoptosis. Cells lacking topo IIbeta were resistant to selenite-induced cell growth inhibition, suggesting that this isoenzyme is a target for selenite. We report for the first time that selenite induces topo I-DNA complexes in K562 cells; the levels of these complexes were high at short exposure times and seem to appear before the induction of apoptosis. Overall, our results show that selenite induces topo-DNA complexes in cells with both topo I and II, and support previous data that suggest that this agent has potential for the treatment of cancer. (c) 2008 Wiley-Liss, Inc.
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