Antizyme induction mediates feedback limitation of the incorporation of specific polyamine analogues in tissue culture.

ABSTRACT: Spermidine, spermine and putrescine are essential for mammalian cell growth, and there has been a pervasive effort to synthesize analogues of these polyamines that will disrupt their function and serve as tools to inhibit cell proliferation. Recently, we demonstrated that a number of such polyamine analogues are also capable of inducing the regulatory protein AZ (antizyme). In the present study the incorporation of a few sample analogues [mimics of bis(ethyl)spermine] was shown to be significantly limited by a decrease in the V(max) for the polyamine transport system in response to analogue-induced AZ. This creates an unusual circumstance in which compounds that are being designed for therapeutic use actually inhibit their own incorporation into targeted cells. To explore the impact of thi

SUBMITTER: Mitchell JL 

PROVIDER: S-EPMC1134110 | biostudies-literature | 2004 Dec

REPOSITORIES: biostudies-literature