S-adenosylmethionine decarboxylase activity and utilization of exogenous putrescine are enhanced in colon cancer cells stimulated to grow by EGF.
Polyamines spermidine and spermine and their precursor putrescine are necessary for cell growth. Polyamine content is high in rapidly growing malignant cells, due to enhanced putrescine synthesis by ornithine decarboxylase (ODC), and increased uptake. In contrast to other cells of the body, colon cancer cells are exposed to high putrescine concentrations from the lumen.


OBJECTIVE
To investigate the utilization of luminal putrescine in colon cancer, we studied the effect of a potent mitogen, epidermal growth factor (EGF), on the activity of the enzyme responsible for putrescine conversion, S-adenosylmethionine decarboxylase (SAMDC), in Caco-2 cells.


METHODS
Cell counts, ODC and SAMDC activities and intracellular polyamines were evaluated in the presence and absence of exogenous putrescine in concentrations resembling those normally present in the colonic lumen.


RESULTS
ODC and SAMDC activity and putrescine uptake were strongly stimulated by EGF. Both synthesized and absorbed putrescine was rapidly converted to spermidine and spermine after EGF. Conversion pattern was identical in the cells stimulated with EGF only and EGF plus exogenous putrescine, indicating that, if stimulated to proliferate, colon cancer cells utilize the entire available putrescine pool. SAMDC inhibitor, methylglyoxal-bis-guanylhydrazone, induced growth arrest which was not reversed by exogenous putrescine, but only by high concentrations of spermidine.


CONCLUSIONS
Enhanced proliferation in colon cancer cells is associated with increased SAMDC activity and rapid conversion of putrescine to spermidine and spermine. SAMDC might be a preferable target for therapeutic attempts to impair growth by reducing intracellular polyamine pools in colon cancer.
Milovic
V
V
2nd Department of Medicine, Johann Wolfgang Goethe University, Frankfurt, Germany.
Turhanowa
L
L
Fares
F A
FA
Lerner
A
A
Caspary
W F
WF
Stein
J
J
D012437:Adenosylmethionine Decarboxylase / Q000378:metabolism*; D018938:Caco-2 Cells; D002455:Cell Division / Q000187:drug effects* / Q000502:physiology; D003110:Colonic Neoplasms / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D006801:Humans; D009955:Ornithine Decarboxylase / Q000378:metabolism; D011700:Putrescine / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D013095:Spermidine / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000201:enzymology
D011994:Recombinant Proteins; D004815:Epidermal Growth Factor; D009955:Ornithine Decarboxylase; D012437:Adenosylmethionine Decarboxylase; D013095:Spermidine; D011700:Putrescine