Apomorphine has a potent antiproliferative effect on Chinese hamster ovarycells

Apomorphine is a potent non selective agonist at the D-1 and D-2 dopamine r eceptors acting both pre- and post-synaptically, In this report we describe a novel function of apomorphine, independent from its dopaminergic activit y. Apomorphine inhibits Chinese hamster ovary (CHO)-K1 cell proliferation i n a dose-dependent manner. The EC50 of apomorphine-induced inhibition of CH O-K1 cell proliferation determined by cell counting was 3.24 +/- 0.07 mu M. Remarkably, the dose-response curve obtained by measuring the incorporatio n of [H-3]thymidine was practically identical to the previous one giving an EC50 of 3.52 +/- 0.04 mu M. The dopaminergic antagonists SCH23390 and spip erone at a concentration of 10 mu M (well beyond their K-d values for the d opamine D-1- and D-2-like receptors respectively) were not able to antagoni ze the effect of apomorphine on CHO-K1 cell proliferation. Apomorphine exer ts its effect early during incubation; CHO-K1 cells exposed to apomorphine for a period as short as Ih and then allowed to grow for three days were si gnificantly reduced in number with respect to untreated control cells. Afte r four hours of exposition to apomorphine (10 mu M) the antiproliferative e ffect was similar to that seen when this compound was present in the bath f or all three days. Concentrations of apomorphine higher than 10 mu M induce d cell death, and the colony was completely destroyed at 50 mu M. Cytometri c analyses showed a significant accumulation of CHO-K1 cells in the G2/M ph ase.