Atrial Natriuretic Peptide and Long Acting Natriuretic Peptide Inhibit ERK 1/2 in Prostate Cancer Cells

Abstract

Background: Atrial natriuretic peptide (ANP) and long acting natriuretic peptide (LANP) have anticancer effects in human prostate adenocarcinomas. Materials and Methods: ANP, LANP and cyclic GMP's effects on extracellular signal-regulated kinase (ERK) 1/2 kinase were examined in human prostate adenocarcinoma cells. Results: ANP and LANP decreased the activation of ERK 1/2 over a concentration range of 0.01 μM to 10 μM. ANP and LANP's maximal inhibition of the phosphorylation of ERK 1/2 kinase were 94% and 88% (p<0.0001), respectively. ANP had significant effects within five min at its 10 μM concentration. The inhibition of ERK 1/2 lasted for at least two h, where it was maximal, secondary to both peptides. Their ability to inhibit ERK 1/2 was inhibited by cyclic GMP antibody and cyclic GMP itself inhibited ERK 1/2 phosphorylation. Conclusion: ANP and LANP both inhibit ERK 1/2 kinase mediated via cyclic GMP as part of their anticancer mechanism(s) of action.