Vessel Dilator and Kaliuretic Peptide Inhibit MEK 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: The effect of vessel dilator, kaliuretic peptide and cyclic GMP on MEK 1/2 kinase were examined in human prostate adenocarcinoma cells. Results: Vessel dilator and kaliuretic peptide decreased the activation of MEK 1/2 over a concentration range of 0.01 μM to 10 μM. Vessel dilator and kaliuretic peptide (each 10 μM) inhibited the phosphorylation of MEK 1/2 kinase by 98% (p<0.0001) and 81% (p<0.001), respectively. The inhibition of MEK 1/2 lasted for at least two hours, where it was maximal, secondary to both peptides. Their ability to inhibit MEK 1/2 was inhibited by cyclic GMP antibody and cyclic GMP itself inhibited MEK 1/2 phosphorylation. Conclusion: Vessel dilator and kaliuretic peptide both inhibit MEK 1/2 kinase mediated via cyclic GMP as part of their anticancer mechanism(s) of action.