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Curcumin induces high levels of topoisomerase I- and II-DNA complexes in K562 leukemia cells

Lookup NU author(s): Dr Miguel Lopez-Lazaro, Dr Elaine Willmore, Andrew Jobson, Kathryn Gilroy, Hannah Curtis, Dr Kay Padget, Professor Caroline Austin

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Abstract

Recent data suggest that curcumin, a phytochemical with cancer chemopreventive potential, might be useful in the treatment of several solid and hematological malignancies. DNA topoisomerases (topos) are the target of several drugs commonly used in cancer chemotherapy. These drugs induce topo-DNA complexes with either topo I or topo II; then cellular processing converts these complexes into permanent DNA strand breaks that trigger cell death. Using the TARDIS in vivo assay, this study shows for the first time that curcumin induces topo I and topo II (α and β)-DNA complexes in K562 leukemia cells. A comparative analysis revealed that the levels of these complexes were higher than those induced by several standard topo I and topo II inhibitors at equitoxic doses. Curcumin-induced topo I and topo II-DNA complexes were prevented by the antioxidant N-acetylcysteine; this suggests that, unlike the standard topo inhibitors, reactive oxygen species may mediate the formation of these complexes. Overall, this work shows that curcumin is capable of inducing topo-DNA complexes in cells with both topo I and topo II and increases the evidence suggesting that this dietary agent has potential to be tested in cancer chemotherapy. © 2007 American Chemical Society and American Society of Pharmacognosy.


Publication metadata

Author(s): López-Lázaro M, Willmore E, Jobson AG, Gilroy KL, Curtis H, Padget K, Austin CA

Publication type: Article

Publication status: Published

Journal: Journal of Natural Products

Year: 2007

Volume: 70

Issue: 12

Pages: 1884-1888

ISSN (print): 0163-3864

ISSN (electronic): 1520-6025

Publisher: American Chemical Society

URL: http://dx.doi.org/10.1021/np070332i

DOI: 10.1021/np070332i

PubMed id: 18076140


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