Curcumin induces high levels of topoisomerase I- and II DNA complexes in K562 leukemia cells
Curcumin induces high levels of topoisomerase I- and II DNA complexes in K562 leukemia cells
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DOI：
10.1021/np070332i
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发表时间：
2007-12-01
影响因子：
5.1
通讯作者：
Austin, Caroline A.
中科院分区：
文献类型：
--
作者：
Lopez-Lazaro, Miguel;Willmore, Elaine;Austin, Caroline A.
最近的数据表明，姜黄素，一种具有癌症化学预防潜力的植物化学物质，可能在治疗几种固体和血液系统恶性肿瘤方面有用。DNA拓扑异构酶(TOPO)是癌症化疗中常用的几种药物的靶标。这些药物诱导与Topo I或Topo II的Topo-DNA复合体，然后细胞处理将这些复合体转化为永久性的DNA链断裂，从而触发细胞死亡。用TARDIS体内实验首次表明姜黄素诱导K562白血病细胞Topo I和Topo II((α和β)-DNA复合体)。比较分析表明，在等毒性剂量下，这些复合体的水平高于几种标准Topo I和Topo II抑制剂诱导的水平。抗氧化剂N-乙酰半胱氨酸可以阻止姜黄素诱导的Topo I和Topo II-DNA复合体的形成；这表明，与标准的Topo抑制剂不同，活性氧可能参与了这些复合体的形成。总体而言，这项工作表明，姜黄素能够在同时具有Topo I和Topo II的细胞中诱导Topo-DNA复合体，并增加了这种饮食制剂有可能在癌症化疗中进行测试的证据。
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 ((alpha and beta)-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.