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Lookup NU author(s): Professor Caroline AustinORCiD, Dr Miguel Lopez-Lazaro
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The alpha, beta-unsaturated lactones 2-furanone and 2-pyrone are part of the chemical structure of a variety of naturally occurring compounds (e.g., cardenolides, bufadienolides, acetogenins, coumarins, and food-flavoring furanones), some of which have shown anticancer activity and/or DNA damaging effects. Here we report that 2-furanone and 2-pyrone induce cellular DNA damage (assessed by the comet assay and the gamma-H2AX focus assay) and the formation of topoisomerase I- and topoisomerase IIDNA complexes in cells (visualized and quantified in situ by the TARDIS assay). Cells mutated in BRCA2 (deficient in homologous recombination repair) were significantly hypersensitive to the cytotoxic activity of 2-pyrone, therefore suggesting that BRCA2 plays an important role in the repair of DNA damage induced by this lactone. Both lactones were cytotoxic in A549 lung cancer cells at lower concentrations than in MRC5 non-malignant lung fibroblasts. The possible involvement of 2-furanone and 2-pyrone in the anticancer and DNA-damaging activities of compounds containing these lactones is discussed. (C) 2013 Elsevier Ireland Ltd. All rights reserved.
Author(s): Calderon-Montano JM, Burgos-Moron E, Orta ML, Pastor N, Austin CA, Mateos S, Lopez-Lazaro M
Publication type: Article
Publication status: Published
Journal: Toxicology Letters
Year: 2013
Volume: 222
Issue: 1
Pages: 64-71
Print publication date: 15/07/2013
ISSN (print): 0378-4274
ISSN (electronic): 1879-3169
Publisher: Elsevier Ireland
URL: http://dx.doi.org/10.1016/j.toxlet.2013.07.007
DOI: 10.1016/j.toxlet.2013.07.007
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