PT - JOURNAL ARTICLE AU - L Ghoda AU - H S Basu AU - C W Porter AU - L J Marton AU - P Coffino TI - Role of ornithine decarboxylase suppression and polyamine depletion in the antiproliferative activity of polyamine analogs. DP - 1992 Aug 01 TA - Molecular Pharmacology PG - 302--306 VI - 42 IP - 2 4099 - http://molpharm.aspetjournals.org/content/42/2/302.short 4100 - http://molpharm.aspetjournals.org/content/42/2/302.full SO - Mol Pharmacol1992 Aug 01; 42 AB - Two transfected cell lines, one carrying a mammalian ornithine decarboxylase (ODC) that is suppressed by polyamines and one carrying a trypanosomal ODC that is not, were used to ask whether ODC suppression is necessary for the antiproliferative activities of two polyamine analogs, N1,N8-bis(ethyl)spermidine (BES) and N1,N14-bis(ethyl)homospermine (BE444). Both analogs accumulated within cells and suppressed S-adenosylmethionine decarboxylase, as well as polyamine-sensitive mouse ODC activity. Neither drug was able to suppress the activity of the polyamine-refractory trypanosome ODC. But, whereas BE444 was able to inhibit growth of both cell lines, BES could inhibit only growth of cells carrying the polyamine-sensitive ODC, under conditions that cause prolonged depletion of endogenous polyamines. We conclude from these studies that the antiproliferative activity of BES, a less potent drug, requires the suppression of ODC. The efficacy of BE444 is enhanced by its ability to suppress ODC. However, it can function without ODC suppression, whereas BES cannot.