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Inhibitory effect of conjugated eicosapentaenoic acid on mammalian DNA polymerase and topoisomerase activities and human cancer cell proliferation.

Abstract：

: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 (LD(50)=20.0 microM), and the inhibitory effect was stronger than that of non-conjugated EPA. cEPA arrested the cells at G1/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.

journal_name

Biochem Pharmacol

journal_title

Biochemical pharmacology

authors

Yonezawa Y,Hada T,Uryu K,Tsuzuki T,Eitsuka T,Miyazawa T,Murakami-Nakai C,Yoshida H,Mizushina Y

doi

10.1016/j.bcp.2005.05.008

subject

Has Abstract

pub_date

2005-08-01 00:00:00

pages

453-60

issue

3

eissn

0006-2952

issn

1873-2968

pii

S0006-2952(05)00321-7

journal_volume

70

pub_type

杂志文章

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