Cantero G, Campanella C, Mateos S, Cortés F
Department of Cell Biology, Faculty of Biology, University of Seville Seville, Spain.
Mutagenesis. 2006 Sep;21(5):321-5. doi: 10.1093/mutage/gel033. Epub 2006 Sep 1.
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.
木犀草素和槲皮素是广泛分布的植物类黄酮，具有多种化学和生物学活性，包括清除自由基和抗氧化活性。最近，有报道称这两种类黄酮均能抑制DNA拓扑异构酶I和II（拓扑异构酶I和拓扑异构酶II），这一特性连同它们诱导DNA和染色体损伤的能力，使它们成为候选抗癌化合物。在本研究中，我们通过比较它们对中国仓鼠卵巢AA8细胞拓扑异构酶II活性的影响，证实了这两种化合物均为拓扑异构酶II抑制剂。由于干扰拓扑异构酶II在复制末期解决DNA缠结的功能会导致有丝分裂时染色体错误分离，我们研究了木犀草素和槲皮素是否能有效诱导AA8细胞内复制。抑制拓扑异构酶II催化活性的木犀草素和槲皮素浓度导致出现双染色体中期的产率异常高。鉴于多倍体通过非整倍体和遗传不稳定性与肿瘤发展之间已确立的关系，这些结果对木犀草素和槲皮素在癌症治疗中的实用性提出了质疑。
