Effect of N1,N12-bis(ethyl)spermine and related compounds on growth and polyamine acetylation, content, and excretion in human colon tumor cells.
Exposure of human colon tumor (HT 29 cells) to N1,N12-bis(ethyl)spermine and analogs produced a rapid loss of intracellular polyamines. This loss was brought about predominantly by an increased excretion of spermidine. N1,N11-Bis(ethyl)norspermine and N1,N12-Bis(ethyl)spermine were potent inducers of spermidine/spermine N1-acetyltransferase, and this induction facilitated the efflux of polyamines by enhancing the conversion of spermine into spermidine. N1,N14-Bis(ethyl)homospermine, which did not induce spermidine/spermine N1-acetyltransferase, also caused the loss of spermidine from the cell but was less effective in bringing about the decline in intracellular spermine. These results indicate that cellular polyamine levels can be regulated by excretion of spermidine and that the bis(ethyl)spermine derivatives deplete intracellular polyamine content by interference with this process.
Pegg
A E
AE
Department of Physiology, Milton S. Hershey Medical Center, Pennsylvania State University College of Medicine, Hershey 17033.
Wechter
R
R
Pakala
R
R
Bergeron
R J
RJ
D000107:Acetylation; D000123:Acetyltransferases / Q000378:metabolism; D003110:Colonic Neoplasms / Q000378:metabolism*; D006801:Humans; D011073:Polyamines / Q000378:metabolism*; D011874:Radiometry; D013096:Spermine / Q000031:analogs & derivatives* / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000378:metabolism; D000099228:Diamine N-Acetyltransferase
D000123:Acetyltransferases; D011073:Polyamines; D013096:Spermine; D000099228:Diamine N-Acetyltransferase; C052614:N(1), N(12)-diethylspermine