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- W93671543 abstract "Cancer therapeutic drugs that inhibit DNA topoisomerase (topo) II by stabilizing the cleavable complex are collectively known as topo II poisons. Phenoxodiol is a synthetic derivative of the plant isoflavone daidzein and is currently undergoing clinical testing as a cancer therapeutic drug. The development of this agent as an antitumor drug was based to a large extent on its low toxicity in normal tissues but potent topo II inhibitory effects in rapidly dividing tumor cells. To evaluate phenoxodiol as a potential inhibitor of topoisomerases, we used the relaxation and nicking assays that can identify topo I inhibitors, and the unknotting and DNA cleavage assays that can identify topo II inhibitors. Phenoxodiol inhibited the catalytic activity of topo II in a dose-dependent manner and it stabilized the topo II-mediated cleavable complex, demonstrating that this agent is a topo II poison. Phenoxodiol's topo II inhibitory effects were comparable to those of other antitumor agents such as VP-16 and were stronger than those of genistein. Phenoxodiol did not inhibit topo I catalytic activity nor did it stabilize the topo I-mediated cleavable complex. These results demonstrate that phenoxodiol is a topo II-specific poison and suggest that this novel agent may find applications in cancer chemotherapy." @default.
- W93671543 created "2016-06-24" @default.
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- W93671543 date "2003-01-18" @default.
- W93671543 modified "2023-09-23" @default.
- W93671543 title "Phenoxodiol (2H-1-benzopyran-7-0,1,3-(4-hydroxyphenyl)), a novel isoflavone derivative, inhibits DNA topoisomerase II by stabilizing the cleavable complex." @default.
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