Effect of polyamine analogues and inhibition of polyamine oxidase on spermidine/spermine N¹-acetyltransferase activity and cell proliferation

Several bis(ethyl)polyamine analogues are currently undergoing trials as antitumor agents. The ability of some of these analogues to induce spermidine/spermine N¹-acetyltransferase and to inhibit cell proliferation was examined in a number of different cell lines. Although N¹,N¹¹ bis(ethyl)norspermine was a potent inducer of the acetylase in all cell lines tested, there was a striking difference in the acetylase induction in response to N¹,N¹¹-bis(ethylamino)propyl]-1,7-heptanediamine. This was a very strong inducer in CHO cells but had no effect in HT29 cells and very little effect in COS-7 or L1210 cells. There was no correlation between the induction of the acetylase and the ability of these analogues to inhibit cell proliferation since N¹, N¹¹-bis(ethylamino)-propyl]-1,7-heptanediamine was as at least as strongly antiproliferative as N¹,N¹¹-bis(ethyl)-norspermine or N¹,N¹²-bis(ethyl)spermine. Acetylase induction and the intracellular level of the analogues were increased in CHO cells by treatment with a polyamine oxidase inhibitor suggesting that they are degraded by polyamine oxidase. The absence of polyamine oxidase in some tumors may therefore contribute to their sensitivity to these analogues.