Significant induction of spermidine/spermine N1-acetyltransferase without cytotoxicity by the growth-supporting polyamine analogue 1,12-dimethylspermine.
The superinduction of the polyamine catabolic enzyme spermidine/spermine N1-acetyltransferase (SSAT) has been implicated in the cell type-specific cytotoxic activity of some polyamine analogues. We now report that one polyamine analogue, 1,12-dimethylspermine (DMSpm), produces a large induction of SSAT with no significant effects on growth in the human large cell lung carcinoma line, NCl H157. This cell line has been demonstrated to respond to other analogues with SSAT superinduction and cell death. Treatment of the lung cancer cell line with DMSpm produces a rapid increase in SSAT activity and a near complete depletion of the natural polyamines. Additionally, DMSpm supports cell growth in cells which have been depleted of their natural polyamines by the ornithine decarboxylase inhibitor, 2-difluoromethylornithine. The current results suggest that significant induction of SSAT can occur in the absence of cytotoxicity when the inducing polyamine analogue can support growth and that increased SSAT activity alone is not sufficient for cytotoxicity to occur.
Yang
J
J
Oncology Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA.
Xiao
L
L
Berkey
K A
KA
Tamez
P A
PA
Coward
J K
JK
Casero
R A
RA
D000123:Acetyltransferases / Q000096:biosynthesis*; D002470:Cell Survival / Q000187:drug effects; D000518:Eflornithine / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects*; D015870:Gene Expression / Q000187:drug effects; D066298:In Vitro Techniques; D009955:Ornithine Decarboxylase / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D013096:Spermine / Q000031:analogs & derivatives* / Q000494:pharmacology; D013997:Time Factors; D014407:Tumor Cells, Cultured; D000099228:Diamine N-Acetyltransferase
D000123:Acetyltransferases; D000518:Eflornithine; D009955:Ornithine Decarboxylase; D012333:RNA, Messenger; D013096:Spermine; D000099228:Diamine N-Acetyltransferase; C073195:1,12-dimethylspermine