Journal
BIOCHEMICAL PHARMACOLOGY
Volume 70, Issue 3, Pages 453-460Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bcp.2005.05.008
Keywords
conjugated eicosapentaenoic acid (cEPA); DNA polymerase; enzyme inhibitor; DNA replication; cytotoxicity; cell proliferation; apoptosis
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Conjugated eicosapentaenoic acid (cEPA) selectively inhibited the activities of mammalian DNA polymerases (pols) and human DNA topoisomerases (topos) [Yonezawa Y, Tsuzuki T, Eitsuka T, Miyazawa T, Hada T, Uryu K, et al. Inhibitory effect of conjugated eicosapentaenoic acid on human DNA topoisomerases I and II. Arch Biochem Biophys 2005;435:197-206]. In this report, we investigated the inhibitory effect of cEPA on a human promyelocytic leukemia cell line, HL-60, to determine which enzymes influence cell proliferation. cEPA inhibited the proliferation of HL-60 cells (LD50 = 20.0 mu M), and the inhibitory effect was stronger than that of nonconjugated EPA. cEPA arrested the cells at GI/S-phase, increased cyclin A and E protein levels, and prevented the incorporation of thymidine into the cells, indicating that it blocks the primary step of in vivo DNA replication by inhibiting the activity of replicative pols rather than topos. This compound also induced apoptosis of the cells. These results suggested the therapeutic potential of cEPA as a leading anti-cancer compound that poisons pols. (c) 2005 Elsevier Inc. All rights reserved.
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