Interaction of gallium nitrate with other inhibitors of ribonucleotide reductase: effects on the proliferation of human leukemic cells.
Cancer Lett
; 129(2): 199-204, 1998 Jul 17.
Article
em En
| MEDLINE
| ID: mdl-9719462
ABSTRACT
Ribonucleotide reductase, a key enzyme in deoxyribonucleotide synthesis, is an important target for cancer chemotherapy. Drugs that inhibit its individual components may act synergistically to block DNA synthesis. Prior work has established that gallium inhibits the R2 subunit of ribonucleotide reductase. We show that gallium acts synergistically with the ribonucleotide reductase inhibitors gemcitabine and hydroxyurea to inhibit the proliferation of CCRF-CEM cells. In contrast, combinations of gallium with the ribonucleotide reductase inhibitors amidox, didox, or trimidox produced antagonistic effects on cell growth. Spectroscopy analysis revealed that as a result of their metal-binding properties, amidox, didox and trimidox formed complexes with gallium, thus negating potential synergistic actions. Our results have important implications in the design of clinical trials using these ribonucleotide reductase inhibitors in combination.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ribonucleotídeo Redutases
/
Leucemia-Linfoma Linfoblástico de Células Precursoras
/
Gálio
Limite:
Humans
Idioma:
En
Revista:
Cancer Lett
Ano de publicação:
1998
Tipo de documento:
Article
País de afiliação:
Estados Unidos