Inhibitory effect of conjugated eicosapentaenoic acid on mammalian DNA polymerase and topoisomerase activities and human cancer cell proliferation.
Biochem Pharmacol
; 70(3): 453-60, 2005 Aug 01.
Article
en En
| MEDLINE
| ID: mdl-15963470
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;435197-206]. 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.
Buscar en Google
Colección:
01-internacional
Asunto principal:
Leucemia Promielocítica Aguda
/
Ácido Eicosapentaenoico
/
Inhibidores de la Síntesis del Ácido Nucleico
/
Inhibidores de Topoisomerasa
/
Inhibidores de Crecimiento
/
Antineoplásicos
Límite:
Humans
Idioma:
En
Revista:
Biochem Pharmacol
Año:
2005
Tipo del documento:
Article
País de afiliación:
Japón