Topoisomerase II inhibition and high yield of endoreduplication induced by the flavonoids luteolin and quercetin

Luteolin and quercetin are widely distributed plant flavonoids that possess a variety of chemical and biological activities, including free-radical scavenging and antioxidant activity. Recently, both flavonoids have been reported to inhibit DNA topoisomerases I and II (topo I and topo II), a propert...

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Bibliographic Details
Published in:Mutagenesis 2006-09, Vol.21 (5), p.321-325
Main Authors: Cantero, G., Campanella, C., Mateos, S., Cortés, F.
Format: Article
Language:English
Subjects:
Animals
Antineoplastic Agents - adverse effects
Antineoplastic Agents - pharmacology
Biological and medical sciences
Cells, Cultured
Chromosome Aberrations - chemically induced
Chromosome Segregation - drug effects
Cricetinae
DNA Damage - drug effects
DNA Topoisomerases, Type II - metabolism
Enzyme Inhibitors - pharmacology
Flavonoids - adverse effects
Fundamental and applied biological sciences. Psychology
Luteolin - adverse effects
Models, Biological
Molecular and cellular biology
Molecular genetics
Mutagenesis. Repair
Polyploidy
Quercetin - adverse effects
Topoisomerase II Inhibitors
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Summary:Luteolin and quercetin are widely distributed plant flavonoids that possess a variety of chemical and biological activities, including free-radical scavenging and antioxidant activity. Recently, both flavonoids have been reported to inhibit DNA topoisomerases I and II (topo I and topo II), a property that, together with their ability to induce DNA and chromosome damage, has made them candidate anticancer compounds. In the present study, we confirmed that both compounds are topo II inhibitors by conducting a comparative study of their effect on topo II activity from Chinese hamster ovary AA8 cells. Because interference with the function of topo II to resolve DNA entanglement at the end of replication results in chromosome malsegregation at mitosis, we investigated whether luteolin and quercetin are effective in inducing endoreduplication in AA8 cells. Concentrations of luteolin and quercetin that inhibited topo II catalytic activity resulted in extraordinarily high yields of metaphases showing diplochromosomes. Given the established relationship of polyploidy with tumor development via aneuploidy and genetic instability, these results question the usefulness of luteolin and quercetin in cancer therapy.
ISSN:0267-8357
1464-3804
DOI:10.1093/mutage/gel033