Inhibition of the expression of ornithine decarboxylase by haloperidol in difluoromethylornithine-resistant leukemia cells.
In difluoromethylornithine-resistant L1210 cells stimulated to grow from quiescence, haloperidol caused an early and dose-dependent inhibition of the induction of ornithine decarboxylase (ODC) activity, with an IC50 of 3.5 microM. This effect was accompanied by a reduction in the ODC mRNA level and inhibition of cell growth. Other sigma ligands of different chemical classes inhibited the induction of ODC activity, whereas sulpiride, a dopamine antagonist devoid of sigma-binding affinity, was ineffective. These results indicate that the inhibition of ODC expression may be an early event involved in the antiproliferative response of leukemia cells to haloperidol.
Flamigni
F
F
Dipartimento di Biochimica G. Moruzzi, Università di Bologna, Italy.
Stanic
I
I
Stefanelli
C
C
Muscari
C
C
Giaccari
A
A
Rossoni
C
C
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D014150:Antipsychotic Agents / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D004351:Drug Resistance; D000518:Eflornithine / Q000494:pharmacology*; D004790:Enzyme Induction / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D006220:Haloperidol / Q000494:pharmacology*; D007939:Leukemia L1210 / Q000201:enzymology / Q000235:genetics; D051379:Mice; D009955:Ornithine Decarboxylase / Q000096:biosynthesis* / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D000970:Antineoplastic Agents; D014150:Antipsychotic Agents; D012333:RNA, Messenger; D009955:Ornithine Decarboxylase; D006220:Haloperidol; D000518:Eflornithine