Cell cycle dependent regulation of IMP dehydrogenase activity and effect of tiazofurin.
Life Sci
; 51(16): 1309-15, 1992.
Article
em En
| MEDLINE
| ID: mdl-1357518
ABSTRACT
The activity of IMP dehydrogenase (IMP DH), the rate-limiting enzyme of de novo GTP biosynthesis, was shown to be increased in cancer cells. Tiazofurin, an inhibitor of IMP dehydrogenase, proved to be an effective agent in the treatment of refractory granulocytic leukemia. To examine the cell cycle dependent alterations of GTP synthesis and sensitivities to tiazofurin, we measured IMP DH activities and GTP pools, as well as the effects of tiazofurin on cell cycle phase enriched HL-60 cells. We now show that IMP DH activities and GTP concentrations are increased in S-phase enriched fractions of HL-60 cells. Moreover, the depletion of GTP concentrations by tiazofurin is most effective in S-phase enriched HL-60 cells. These results may be utilized in cancer chemotherapy to combine tiazofurin with biologic response modifiers which recruit quiescent leukemic cells into the cell cycle.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ribavirina
/
Ciclo Celular
/
IMP Desidrogenase
/
Antimetabólitos Antineoplásicos
Limite:
Humans
Idioma:
En
Revista:
Life Sci
Ano de publicação:
1992
Tipo de documento:
Article
País de afiliação:
Áustria