title: Apomorphine, dopamine and phenylethylamine reduce the proportion of phosphorylated insulin receptor substrate 1.
abstract: We tested the ability of dopamine, apomorphine, phenylethylamine and pergolide to inhibit the proliferation of fetal calf serum-stimulated human breast cancer (MCF)-7 cells. While the first three compounds were able to block the proliferation of MCF-7 cells, pergolide failed to do so (up to 100 microM). The inhibitory effect of dopamine, apomorphine and phenylethylamine was also evident in serum-starved insulin-stimulated MCF-7 cells. Apomorphine also inhibited the proliferation of the human oestrogen receptor-negative breast cancer (MDA-MB231) and prostate carcinoma (LNCaP) cell lines. In a second set of experiments, we measured the ability of dopamine, apomorphine, phenylethylamine and pergolide to inhibit the phosphorylation (or increase the dephosphorylation) of the insulin receptor substrate (IRS)-1, a major intracellular substrate of the insulin-like growth factor (IGF)-1 receptor. Dopamine, apomorphine and phenylethylamine all reduced to zero the level of phosphorylated IRS-1 with potencies ranging between 0.01 and 1 microM. Finally, we found that fibroblasts from IRS-1 null (-/-) mice were less sensitive to the anti-proliferative effect of apomorphine compared to fibroblasts from wild type-mice, suggesting that the inhibition of IRS-1 phosphorylation by apomorphine is an important aspect of the activity of this compound.
authors.affiliation: Department of Clinical and Experimental Pharmacology, University of Catania, Catania, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Chiarenza
authors.forename: M
authors.initials: M
authors.lastname: Scarselli
authors.forename: F
authors.initials: F
authors.lastname: Novi
authors.forename: L
authors.initials: L
authors.lastname: Lempereur
authors.forename: R
authors.initials: R
authors.lastname: Bernardini
authors.forename: G U
authors.initials: GU
authors.lastname: Corsini
authors.forename: R
authors.initials: R
authors.lastname: Maggio
mesh_terms: D001058:Apomorphine / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D004298:Dopamine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D055504:Insulin Receptor Substrate Proteins; D010479:Pergolide / Q000494:pharmacology; D010627:Phenethylamines / Q000494:pharmacology*; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D014407:Tumor Cells, Cultured
chemical_list: C526292:IRS1 protein, human; D055504:Insulin Receptor Substrate Proteins; C526295:Irs1 protein, mouse; D010627:Phenethylamines; D010750:Phosphoproteins; D010479:Pergolide; D001058:Apomorphine; D004298:Dopamine