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 N,N'-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.
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Department of Cell and Molecular Physiology, M.S. Hershey Medical Center, Pennsylvania State University College of Medicine, Hershey 17033, USA.
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D000123:Acetyltransferases / Q000378:metabolism*; D000818:Animals; D016466:CHO Cells; D002455:Cell Division / Q000187:drug effects*; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D006224:Cricetinae; D004790:Enzyme Induction / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000037:antagonists & inhibitors*; D011073:Polyamines / Q000494:pharmacology*; D000097667:Polyamine Oxidase; D000099228:Diamine N-Acetyltransferase
D000123:Acetyltransferases; D000587:Oxidoreductases Acting on CH-NH Group Donors; D011073:Polyamines; D000097667:Polyamine Oxidase; D000099228:Diamine N-Acetyltransferase