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

Yuko Yonezawa, Takahiko Hada, Keisuke Uryu, Tsuyoshi Tsuzuki, Takahiro Eitsuka, Teruo Miyazawa, Chikako Murakami-Nakai, Hiromi Yoshida, Yoshiyuki Mizushina

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)

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 (LD50 = 20.0 μM), 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.

Original languageEnglish
Pages (from-to)453-460
Number of pages8
JournalBiochemical Pharmacology
Volume70
Issue number3
DOIs
Publication statusPublished - 2005 Aug 1

Keywords

  • Apoptosis
  • Cell proliferation
  • Conjugated eicosapentaenoic acid (cEPA)
  • Cytotoxicity
  • DNA polymerase
  • DNA replication
  • Enzyme inhibitor

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology

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