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Abstract Title:

The dietary anticancer agent ellagic acid is a potent inhibitor of DNA topoisomerases in vitro.

Abstract Source:

Nutr Cancer. 1995 ;23(2):121-30. PMID: 7644381

Abstract Author(s):

A Constantinou, G D Stoner, R Mehta, K Rao, C Runyan, R Moon

Article Affiliation:

A Constantinou

Abstract:

Ellagic acid and 12 related agents have been tested for their ability to inhibit the activities of human DNA topoisomerase (topo) I and II. Using specific in vitro assays, we found ellagic acid and flavellagic acid to be potent inhibitors of the catalytic activities of the two topoisomerases. The minimum concentration required to inhibit>or = 50% of catalytic activity (IC50) of ellagic acid was determined at 0.6 and 0.7 micrograms/ml for topo I and topo II, respectively. Flavellagic acid's IC50 was determined at 3.0 and 3.6 micrograms/ml for topo I and topo II, respectively. Unlike topoisomerase poisons, these two plant phenols did not trap the enzyme-DNA reaction intermediate, known as the cleavable complex. In contrast, ellagic acid prevented other topo I and topo II poisons from stabilizing the cleavable complex, suggesting that the mode of its action is that of an antagonist. Structure-activity studies identified the 3,3'-hydroxyl groups and the lactone groups as the most essential elements for the topoisomerase inhibitory actions of plant phenols. On the basis of these findings and other properties of ellagic acid, a mechanistic model for the documented anticarcinogenic effects of the agent is proposed.

Study Type : In Vitro Study

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Sayer Ji
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