INHIBITION OF THE EXPRESSION OF ORNITHINE DECARBOXYLASE BY HALOPERIDOL IN DIFLUOROMETHYLORNITHINE-RESISTANT LEUKEMIA-CELLS

In difluoromethylornithine-resistant L1210 cells stimulated to grow fr om quiescence, haloperidol caused an early and dose-dependent inhibiti on of the induction of ornithine decarboxylase (ODC) activity, with an IC50 of 3.5 mu M. This effect was accompanied by a reduction in the O DC mRNA level and inhibition of cell growth. Other sigma ligands of di fferent chemical classes inhibited the induction of ODC activity, wher eas sulpiride, a dopamine antagonist devoid of sigma-binding affinity, was ineffective. These results indicate that the inhibition oi ODC ex pression may be an early event involved in the antiproliferative respo nse of leukemia cells to haloperidol. Copyright (C) 1996 Elsevier Scie nce Inc.