EFFECTS OF DIETHYL SPERMINE ANALOGS IN HUMAN BLADDER-CANCER CELL-LINES IN CULTURE

The biochemical and antiproliferative effects of two recently develope d N-alkylated analogues of naturally-occurring polyamines, N1,N14-diet hylhomospermine (DEHSPM) and N1,N11-diethylnorspermine (DENSPM), were investigated in two human transitional cell carcinoma (TCC) lines, T24 and J82. Parallel studies with the ornithine decarboxylase enzyme inh ibitor alpha-difluoromethylornithine (DFMO) were included for comparis on. DENSPM displayed greater antiproliferative activity than DEHSPM in both TCC cell lines. Both analogues were strikingly more potent than DFMO. DEHSPM and DENSPM suppressed the activity of the major biosynthe tic enzymes, ornithine decarboxylase and S-adenosylmethionine decarbox ylase. However, differences in the resulting polyamine depletion sugge st that the substantial antiproliferative activity of these analogues may result from mechanisms other than polyamine depletion. The greater polyamine depletion seen with DENSPM is thought to result from its st riking induction of spermidine/spermine N1-acetyltransferase. DENSPM i s an attractive agent for further preclinical and clinical development , possibly as a chemopreventive agent, in TCC of the bladder.