Atrial Natriuretic Peptide and Long Acting Natriuretic Peptide Inhibit MEK 1/2 Activation in Human Prostate Cancer Cells

Abstract

Background: Atrial natriuretic peptide and long acting natriuretic peptide have anticancer effects in human prostate adenocarcinomas. Materials and Methods: Atrial natriuretic peptide, long acting natriuretic peptide and cyclic GMP's effects on MEK 1/2 kinase were examined in human prostate adenocarcinoma cells. Results: Atrial natriuretic peptide and long acting natriuretic peptide decreased the activation of MEK 1/2 over a concentration range of 0.01 μM to 10 μM. Long acting natriuretic peptide and atrial natriuretic peptide (each 10 μM) inhibited the phosphorylation of MEK 1/2 kinase 97% (p<0.00001) and 88% (p<0.00001), respectively. The inhibition of MEK 1/2 was maximal at two hours, and ceased by four hours, secondary to both peptides. The ability of peptides to inhibit MEK 1/2 was inhibited by cyclic GMP antibody and cyclic GMP itself inhibited MEK 1/2 phosphorylation by 93%. Conclusion: Atrial natriuretic peptide and long acting natriuretic peptide both inhibit MEK 1/2 kinase mediated via cyclic GMP as part of their anticancer mechanism(s) of action.