DIFFERENTIAL INHIBITORY EFFECTS OF 3 NITRIC-OXIDE DONORS ON ORNITHINEDECARBOXYLASE ACTIVITY IN HUMAN COLON-CARCINOMA CELLS

Ornithine decarboxylase (ODC, EC 4.1.1.17) is the enzyme responsible f or the synthesis of polyamines, which are absolutely necessary. for ce ll proliferation. In the present work, we tested the effects of 3 nitr ic oxide (NO) donors, namely, sodium nitroprusside (SNP), (Z)-1-(N-met hyl-N-[6-(N-methylammoniohexyl)amino] diazen-1-ium-1,2-diolate (MAHMA/ NO) and 1,1-diethyl-2-hydroxy-2-nitroso-hpdrazine sodium (DEA/NO), on ODC activity in human colon carcinoma cells (HT-29). SNP was the most effective inhibitor of ODC activity with a concentration of 8 mu mol/L inducing 50% inhibition of basal activity. The effect of SNP was reve rsed by haemoglobin (Hb), but not by GSH or L-cysteine (CYS). Very lit tle of the SNP in solution was degraded into nitrite, but the presence of cellular homogenate increased the production of nitrite. MAHMA/NO and DEA/NO were much less effective than SNP as ODC inhibitors, since the concentrations of these agents which induce 50% inhibition of basa l activity were 20- to 60-fold higher than that of SNP. The effects of MAHMA/NO and DEA/NO were not reversed by haemoglobin. In solution, th ese latter 2 agents were totally degraded into nitrites. In conclusion , SNP on the one hand and MAHMA/NO and DEA/NO on the other appeared to release different NOx species with different efficiency on ODC activi ty. (C) 1998 Elsevier Science Inc.