Antizyme and antizyme inhibitor activities influence cellular responses to polyamine analogs.
Amino Acids
; 33(2): 291-7, 2007 Aug.
Article
em En
| MEDLINE
| ID: mdl-17410332
ABSTRACT
Close structural analogs of spermidine and spermine, polyamine mimetics, are potential chemotheraputic agents as they depress cellular polyamines required for tumor growth. Specific mimetic analogs stimulate synthesis of the regulatory protein antizyme (AZ), which not only inactivates the initial enzyme in polyamine biosynthesis but also inhibits cellular uptake of polyamines. The role of AZ induction in influencing cellular uptake of representative analogs was investigated using three analogs produced by Cellgate Inc., CGC-11047, CGC-11102, and CGC-11144, which exhibit markedly distinct AZ-inducing potential. An inverse correlation was noted between the AZ-inducing activity of a compound and the steady-state levels accumulated in cells. As some tumor cells over express AZI as a means of enhancing the polyamines required for aggressive growth, analog sensitivity was examined in transgenic CHO cells expressing exogenous antizyme inhibitor protein (AZI). Although AZI over expression increased cell sensitivity to analogs, the degree of this affect varied with the analog used.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Poliaminas
/
Proteínas
/
Proteínas de Transporte
Limite:
Animals
Idioma:
En
Revista:
Amino Acids
Assunto da revista:
BIOQUIMICA
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
Estados Unidos