Phytochemicals are a rich source of anticancer drugs and chemopreventive agents. Several of these chemicals appear to exert at least some of their effects through interactions with topoisomerase II, an essential enzyme that regulates DNA supercoiling and removes knots and tangles from the genome. Topoisomerase II-active phytochemicals function by stabilizing covalent protein-cleaved DNA complexes that are intermediates in the catalytic cycle of the enzyme. As a result, these compounds convert topoisomerase II to a cellular toxin that fragments the genome. Because of their mode of action, they are referred to as topoisomerase II poisons as opposed to catalytic inhibitors. The first sections of this article discuss DNA topology, the catalytic cycle of topoisomerase II, and the two mechanisms (interfacial vs. covalent) by which different classes of topoisomerase II poisons alter enzyme activity. Subsequent sections discuss the effects of several phytochemicals on the type II enzyme, including demethyl-epipodophyllotoxins (semisynthetic anticancer drugs) as well as flavones, flavonols, isoflavones, catechins, isothiocyanates, and curcumin (dietary chemopreventive agents). Finally, the leukemogenic potential of topoisomerase II-targeted phytochemicals is described.

中文翻译：

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植物化学物质作为抗癌和化学预防拓扑异构酶 II 毒药。

植物化学物质是抗癌药物和化学预防剂的丰富来源。这些化学物质中的一些似乎通过与拓扑异构酶 II 的相互作用发挥了至少一些作用，拓扑异构酶 II 是一种调节 DNA 超螺旋并从基因组中去除结和缠结的必需酶。拓扑异构酶 II 活性植物化学物质通过稳定共价蛋白裂解的 DNA 复合物发挥作用，该复合物是酶催化循环的中间体。结果，这些化合物将拓扑异构酶 II 转化为细胞毒素，使基因组片段化。由于它们的作用方式，它们被称为拓扑异构酶 II 毒物，而不是催化抑制剂。本文的第一部分讨论了 DNA 拓扑结构、拓扑异构酶 II 的催化循环以及两种机制（界面与非接触）。共价）不同类别的拓扑异构酶 II 毒物改变酶活性。随后的部分讨论了几种植物化学物质对 II 型酶的影响，包括脱甲基表鬼臼毒素（半合成抗癌药）以及黄酮、黄酮醇、异黄酮、儿茶素、异硫氰酸酯和姜黄素（膳食化学预防剂）。最后，描述了拓扑异构酶 II 靶向植物化学物质的致白血病潜力。