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.
All Science Journal Classification (ASJC) codes
- Cancer Research