Antizyme and antizyme inhibitor activities influence cellular responses to polyamine analogs.
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.
Mitchell
J L A
JL
Department of Biological Sciences, Northern Illinois University, DeKalb, IL 60115-2861, USA. jmitchell@niu.edu
Thane
T K
TK
Sequeira
J M
JM
Marton
L J
LJ
Thokala
R
R
D000818:Animals; D015317:Biogenic Polyamines / Q000494:pharmacology; D016466:CHO Cells; D002352:Carrier Proteins / Q000378:metabolism*; D006224:Cricetinae; D003412:Cricetulus; D008114:Liver Neoplasms, Experimental; D011073:Polyamines / Q000494:pharmacology*; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D013096:Spermine / Q000031:analogs & derivatives / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D015317:Biogenic Polyamines; C515675:CGC 11047; C525257:CGC 11102; C505025:CGC-11144; D002352:Carrier Proteins; D011073:Polyamines; D011506:Proteins; C031017:ornithine decarboxylase antizyme; C039317:ornithine decarboxylase antizyme inhibitor; D013096:Spermine