Vessel Dilator and Kaliuretic Peptide Inhibit ERK 1/2 Activation in Human Prostate Cancer Cells

Abstract

Background: Vessel dilator and kaliuretic peptide have anticancer effects in human prostate adenocarcinomas. Materials and Methods: Vessel dilator, kaliuretic peptide and cyclic GMP's effects on ERK 1/2 kinase were examined in human prostate adenocarcinoma cells. Results: Vessel dilator and kaliuretic peptide decreased the activation of ERK 1/2 over a concentration range of 0.01 μM to 1 μM. Vessel dilator and kaliuretic peptide (each 1 μM) inhibited the phosphorylation of ERK 1/2 kinase 96% (p<0.0001) and 70% (p<0.001), respectively. Both had significant effects within five minutes at their 0.01 μM concentrations. The inhibition of ERK 1/2 lasted for at least two hours secondary to both. Their ability to inhibit ERK 1/2 was decreased by cyclic GMP antibody and cyclic GMP itself decreased ERK 1/2 phosphorylation. Conclusion: Vessel dilator and kaliuretic peptide both inhibit ERK 1/2 kinase mediated via cyclic GMP as part of their anticancer mechanism(s) of action.