Oxytocin inhibits the proliferation of MDA-MB231 human breast-cancer cells via cyclic adenosine monophosphate and protein kinase A.
Oxytocin (OT) inhibits the proliferation of breast-cancer cells in vitro via a specific G-coupled receptor. To elucidate the intracellular mechanism involved in this biological effect, different G-coupled receptor mediators have been investigated in untreated and OT-treated MDA-MB231 breast-carcinoma cells. In these cells, after OT treatment, a significant cAMP increase was observed using a radioimmunoassay procedure, whereas the Ca2+ (determined with the fluorescent probe fura-2) and the inositol phosphate (determined after cell labeling with myo(2-(3)H)-inositol) concentrations were not modified, contrary to what has been observed in myometrial and myo-epithelial cells. The PKA inhibitor PKI (6-22) amide reverted the effect of OT, indicating that the anti-proliferative effect of the peptide is strictly related to the cAMP-PKA pathway. OT treatment did not modify tyrosine phosphorylation either. Our results indicate that in breast epithelial cells devoid of contractile activity, cAMP is the intracellular mediator of OT action, whereas the Ca2+-phosphoinositide system is not involved.
Cassoni
P
P
Department of Biomedical Sciences and Oncology, University of Turin, Italy.
Sapino
A
A
Fortunati
N
N
Munaron
L
L
Chini
B
B
Bussolati
G
G
D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D005260:Female; D006801:Humans; D010121:Oxytocin / Q000494:pharmacology* / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects*; D014407:Tumor Cells, Cultured
D010121:Oxytocin; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases